TY - JOUR AU - Abraham,H.D. AU - Aldridge,A.M. AU - Gogia,P. TI - The psychopharmacology of hallucinogens KW - ibogaine KW - drug receptor binding KW - discriminative stimulus KW - animal behavior KW - psychopharmacology KW - instrumental conditioning KW - drug selectivity KW - drug effect KW - binding affinity KW - dose response KW - sedation KW - ataxia KW - nonhuman KW - Male KW - MOUSE KW - animal experiment KW - controlled study KW - intraperitoneal drug administration KW - priority journal KW - article KW - n methyl dextro aspartic acid receptor KW - glutamate receptor agonist KW - Analysis KW - Comparative Study KW - drug dose KW - pd [pharmacology] KW - 3 amino 1 hydroxy 2 pyrrolidinone KW - 1 aminocyclopropanecarboxylic acid KW - cycloserine KW - n methyl dextro aspartic acid receptor blocking agent KW - pd KW - [pharmacology] KW - dizocilpine KW - ifenprodil KW - 2 amino 4,5 (1,2 cyclohexyl) 7 phosphonoheptanoic acid KW - Strychnine KW - Glycine KW - SITES KW - RECEPTORS KW - RECEPTOR COMPLEX KW - COMPLEX KW - Agonists KW - Mice KW - BEHAVIOR KW - Food KW - D-CYCLOSERINE KW - ANTAGONIST KW - HA-966 KW - NMDA Receptor KW - Ion Channels KW - Phencyclidine KW - Hallucinogens JO - Neuropsychopharmacology PY - 1996 AB - The strychnine-insensitive glycine site on the N-methyl-D- aspartate (NMDA) receptor complex is a target for development of a host of therapeutic agents including anxiolytics, antidepressants, antiepileptics, anti-ischemics and cognitive enhancers. In the present experiments, the discriminative stimulus effects of (+)-HA-966 [R-(+)-3-amino-1-hydroxypyrrolid-2- one), a low-efficacy partial agonist of the glycine site, was explored. Male, Swiss-Webster mice were trained to discriminate (+)-HA-966 (170 mg/kg i.p.) from saline in a T- maze under which behavior was controlled by food. Other glycine partial agonists, 1-amino-1-cyclopropanecarboxilic acid and D-cycloserine, fully substituted for the discriminative stimulus effects of (+)-HA-966 despite known differences in other pharmacological effects of these compounds. The glycine site antagonist, 7-chlorkynurenic acid, did not substitute for (+)- HA-966. Likewise other functional NMDA antagonists acting at nonglycine sites of the NMDA receptor also did not substitute: neither the high (dizocilpine) or low affinity (ibogaine) ion-channel blocker, the competitive antagonist, NPC 17742 [2R,4R,5S-2-amino-4,5-(1,2- cyclohexyl)-7-phosphonoheptanoic acid], nor the polyamine antagonist, ifenprodil, substituted for (+)-HA-966. Although the full agonist, glycine, did not substitute, this compound fully blocked the discriminative stimulus effects of (+)-HA-966. In a separate group of mice trained to discriminate 0.17 mg/kg of dizocilpine from saline, (+)-HA-966 produced a maximum of only 50% dizocilpine-appropriate responses. These data suggest that the discriminative stimulus effects of (+)-HA-966 are based upon its partial agonist actions at the strychnine-insensitive glycine site. Furthermore, the lack of substitution of compounds with phencyclidine- like effects (dizocilpine, ibogaine and NPC 17742) or sedative properties (NPC 17742 and (-)-HA-966) suggests that these side-effects may not be part of the subjective effect profile of glycine partial agonists RP - NOT IN FILE SP - 285 EP - 298 VL - 14 ER - TY - JOUR AU - Benwell,M.E.M. AU - Holtom,P.E. AU - Moran,R.J. AU - Balfour,D.J.K. TI - Neurochemical and Behavioral Interactions Between Ibogaine and Nicotine in the Rat KW - ibogaine KW - Nicotine KW - In Vivo Brain Microdialysis KW - Nucleus Accumbens KW - Medial Prefrontal Cortex KW - Striatum KW - Elevated Plus-Maze KW - INVIVO MICRODIALYSIS KW - LOCOMOTOR-ACTIVITY KW - NUCLEUS-ACCUMBENS KW - PREFRONTAL CORTEX KW - Dopamine Release KW - Morphine KW - Cocaine KW - RECEPTORS KW - Serotonin KW - Brain KW - Microdialysis KW - Dopamine KW - Rats KW - Animal KW - RAT KW - Locomotor Activity KW - PRETREATMENT KW - METABOLITES KW - CORTEX KW - DRUGS JO - Brit J Pharmacol PY - 1996 AB - 1 In vivo brain microdialysis has been employed to investigate the effects of ibogaine on nicotine-induced changes in dopamine overflow in the nucleus accumbens (NAc) of freely moving rats. The effects of the compound on locomotor responses to nicotine and behaviour in the elevated plus-maze were also examined. 2 No changes were observed in the dopamine overflow or the locomotor activity of the animals following the administration of ibogaine (40 mg kg(-1), i.p.). However, ibogaine, administered 22 h earlier, significantly (P<0.01) attenuated the increase in dopamine overflow but not the hyperlocomotion, evoked by nicotine. 3 In the elevated plus-maze test, significant reductions in the open:total runway entries in both saline- treated controls (P<0.05) and nicotine-treated (P<0.01) rats were obtained when the animals were tested 22 h after pretreatment with ibogaine (40 mg kg(-1), i.p.). The total activity was significantly (P<0.01) greater in the nicotine-treated rats but this response was not affected by ibogaine pretreatment. 4 Administration of ibogaine was associated with reductions in the tissue levels of 5-hydroxyindoleacetic acid (5-HIAA) in the NAc (P<0.01) and striatum (P<0.05) and an increase in the level of this metabolite in the medial prefrontal cortex (mPFC) (P<0.01) while the levels of dopamine and 5-hydroxytryptamine (5- HT) in the mPFC were reduced (P<0.05). The DOPAC/dopamine (P<0.05) and 5- HIAA/5-HT (P<0.01) ratios were significantly increased in the mPFC for at least 7 days after a single treatment with ibogaine. 5 Ibogaine attenuates the nicotine-induced increases in dopamine overflow in the NAc and may, therefore, inhibit the rewarding effects of this drug. However, the long lasting anxiogenesis induced by ibogaine warrant further investigation before its use could be recommended for smokers RP - IN FILE SP - 743 EP - 749 VL - 117 ER - TY - JOUR AU - Chen,K. AU - Kokate,T.G. AU - Donevan,S.D. AU - Carroll,F.I. AU - Rogawski,M.A. TI - Ibogaine block of the NMDA receptor - in vitro and in vivo studies KW - ibogaine KW - Addiction KW - conditioning KW - craving KW - learning KW - Morphine KW - place preference KW - Reinforcement KW - Reward KW - nmda receptor antagonist.impairs acquisition.rats.mk-801. KW - MEMORY KW - PREFERENCE KW - NMDA Receptor KW - RECEPTORS KW - In Vitro JO - Neuropharmacology PY - 1996 AB - 1. Ibogaine, a proposed anti-addictive agent, has been found to interfere with the acquisition of a weak morphine-induced place preference. The present series of experiments determined if ibogaine would interfere with the expression of a previously established morphine (5 mg/kg) place preference. 2. A single injection of 40 mg/kg of ibogaine 24 h, 12 h or 4 h prior to the preference test (Experiment 1) or 80 mg/kg of ibogaine 24 hr prior to the preference test (Experiment 3) did not interfere with the expression of a morphine conditioned place preference. 3. Furthermore two injections of 40 mg/kg of ibogaine 48 h and 24 h or 24 h and 4 h prior to testing (Experiment 2) did not interfere with the expression of a morphine place preference. 4. Ibogaine appears to be incapable of attenuating the expression of a previously established one-trial morphine place preference. [References: 27] RP - NOT IN FILE SP - 423 EP - 431 VL - 35 ER - TY - JOUR AU - Glick,S.D. AU - Pearl,S.M. AU - Cai,J. AU - Maisonneuve,I.M. TI - Ibogaine Like Effects of Noribogaine in Rats KW - ibogaine KW - Noribogaine KW - Morphine KW - Cocaine KW - Drug Self-Administration KW - Microdialysis KW - Dopamine KW - alkaloid KW - Rats KW - Self Administration KW - Nucleus Accumbens KW - Striatum KW - Tremor KW - Addiction KW - METABOLITES KW - Cocaine Self-Administration KW - Self-Administration KW - Antiaddictive Effects JO - Brain Res PY - 1996 AB - Ibogaine is a naturally occurring alkaloid that has been claimed to be effective in treating addiction to opioids and stimulants; a single dose is claimed to be effective for 6 months. Analogously, studies in rats have demonstrated prolonged (one or more days) effects of ibogaine on morphine and cocaine self- administration even though ibogaine is mostly eliminated from the body in several hours. These observations have suggested that a metabolite may mediate some of the effects of ibogaine. Recently, noribogaine was identified as a metabolite of ibogaine. Accordingly, the present study sought to determine, in rats, whether noribogaine had pharmacological effects mimicking those of ibogaine. Noribogaine (40 mg/kg) was found to decrease morphine and cocaine self-administration, reduce the locomotor stimulant effect of morphine, and decrease extracellular levels of dopamine in the nucleus accumbens and striatum. All of these effects were similar to effects previously observed with ibogaine (40 mg/kg); however, noribogaine did not induce any ibogaine-like tremors. The results suggest that noribogaine may be a mediator of ibogaine's putative anti-addictive effects RP - NOT IN FILE SP - 294 EP - 297 VL - 713 ER - TY - JOUR AU - Glick,S.D. AU - Kuehne,M.E. AU - Maisonneuve,I.M. AU - Bandarage,U.K. AU - Molinari,H.H. TI - 18 Methoxycoronaridine, a Nontoxic Iboga Alkaloid Congener: Effects on Morphine and Cocaine Self Administration and on Mesolimbic Dopamine Release in Rats KW - ibogaine KW - Iboga Alkaloid KW - Methoxycoronaridine KW - Morphine KW - Cocaine KW - Drug Self-Administration KW - PARASAGITTAL ZONES KW - D-AMPHETAMINE KW - Harmaline KW - Tremor KW - alkaloid KW - Addiction KW - Self Administration KW - Rats KW - Purkinje Cells KW - Cerebellum KW - DRUGS KW - Toxicity KW - Self-Administration KW - Dopamine KW - Nucleus Accumbens KW - RELEASE KW - 18 methoxycoronaridine KW - CONGENERS KW - Dopamine Release KW - BEHAVIOR KW - Purkinje Cell JO - Brain Res PY - 1996 AB - Ibogaine, a naturally occurring iboga alkaloid, has been claimed to be effective in treating addiction to opioids and stimulants, and has been reported to inhibit morphine and cocaine self- administration in rats. However, ibogaine also has acute nonspecific side effects (e.g. tremors, decreased motivated behavior in general) as well as neurotoxic effects (Purkinje cell loss) manifested in the vermis of the cerebellum. 18- Methoxycoronaridine (MC) is a novel, synthetic iboga alkaloid congener that mimics ibogaine's effects on drug self- administration without appearing to have ibogaine's other adverse effects. Acutely, in rats, MC decreased morphine and cocaine self- administration but did not affect bar-press responding for water. In some rats, treatment with MC (40 mg/kg) induced prolonged decreases in morphine or cocaine intake lasting several days or weeks. MC had no apparent tremorigenic effect, and there was no evidence of cerebellar toxicity after a high dose (100 mg/kg) of MC. Similar to the effects of ibogaine and other iboga alkaloids that inhibit drug self-administration, MC (40 mg/kg) decreased extracellular levels of dopamine in the nucleus accumbens. MC therefore appears to be a safer, ibogaine- like agent that might be useful in the treatment of addictive disorders RP - NOT IN FILE SP - 29 EP - 35 VL - 719 ER - TY - JOUR AU - Hough,L.B. AU - Pearl,S.M. AU - Glick,S.D. TI - Tissue distribution of ibogaine after intraperitoneal and subcutaneous administration KW - ibogaine KW - Animal KW - Brain Chemistry KW - drug effect KW - Dopamine KW - me [metabolism] KW - hydroxyindoleacetic acid KW - pd [pharmacology] KW - Male KW - Motor Activity KW - Nicotine KW - Rats KW - Rats,Sprague-Dawley KW - Serotonin KW - Support,Non-U.S.Gov't KW - 3,4-Dihydroxyphenylacetic Acid KW - In Vivo Brain Microdialysis KW - Brain KW - Microdialysis KW - Nucleus Accumbens KW - Elevated Plus-Maze KW - Locomotor Activity KW - PRETREATMENT KW - Striatum KW - METABOLITES KW - Medial Prefrontal Cortex KW - PREFRONTAL CORTEX KW - CORTEX KW - DRUGS JO - Life Sci PY - 1996 AB - 1. In vivo brain microdialysis has been employed to investigate the effects of ibogaine on nicotine-induced changes in dopamine overflow in the nucleus accumbens (NAc) of freely moving rats. The effects of the compound on locomotor responses to nicotine and behaviour in the elevated plus-maze were also examined. 2. No changes were observed in the dopamine overflow or the locomotor activity of the animals following the administration of ibogaine (40 mg kg-1, i.p.). However, ibogaine, administered 22 h earlier, significantly (P < 0.01) attenuated the increase in dopamine overflow but not the hyperlocomotion, evoked by nicotine. 3. In the elevated plus-maze test, significant reductions in the open: total runway entries in both saline-treated controls (P < 0.05) and nicotine-treated (P < 0.01) rats were obtained when the animals were tested 22 h after pretreatment with ibogaine (40 mg kg-1, i.p.). The total activity was significantly (P < 0.01) greater in the nicotine-treated rats but this response was not affected by ibogaine pretreatment. 4. Administration of ibogaine was associated with reductions in the tissue levels of 5- hydroxyindoleacetic acid (5-HIAA) in the NAc (P < 0.01) and striatum (P < 0.05) and an increase in the level of this metabolite in the medial prefrontal cortex (mPFC) (P < 0.01) while the levels of dopamine and 5-hydroxytryptamine (5-HT) in the mPFC were reduced (P < 0.05). The DOPAC/dopamine (P < 0.05) and 5-HIAA/5-HT (P < 0.01) ratios were significantly increased in the mPFC for at least 7 days after a single treatment with ibogaine. 5. Ibogaine attenuates the nicotine-induced increases in dopamine overflow in the NAc and may, therefore, inhibit the rewarding effects of this drug. However, the long lasting anxiogenesis induced by ibogaine warrant further investigation before its use could be recommended for smokers RP - NOT IN FILE SP - PL119 EP - PL122 VL - 58 ER - TY - JOUR AU - Ley,F.R. AU - Jeffcoat,A.R. AU - Thomas,B.F. TI - Determination of Ibogaine in Plasma by Gas Chromatography Chemical Ionization Mass Spectrometry KW - ibogaine KW - alkaloid KW - LOCOMOTOR-ACTIVITY KW - Rats KW - Morphine KW - Indoles KW - Pharmacology KW - Methods KW - Pharmacokinetics KW - Metabolism KW - indole alkaloid KW - DRUGS KW - MECHANISMS KW - Recovery JO - J Chromatogr PY - 1996 AB - Ibogaine is a naturally occurring indole alkaloid that is currently being considered as a treatment medication for drug dependence. Although there have been a variety of investigations regarding the mechanisms of action and pharmacology of ibogaine, relatively little has been reported regarding quantitative methods. Because of the paucity of analytical methodologies, studies involving the pharmacokinetics and metabolism of ibogaine have also been limited. A method is described for the determination of ibogaine levels in plasma by gas chromatography- methane chemical ionization mass spectrometry. [(CH3)-C-13-H- 2]Ibogaine was synthesized and used as an internal standard to control for recovery during sample preparation. The assay requires one mi of plasma and is shown to be a selective and sensitive means of ibogaine quantitation RP - NOT IN FILE SP - 101 EP - 109 VL - 723 ER - TY - JOUR AU - Luxton,T. AU - Parker,L.A. AU - Siegel,S. TI - Ibogaine fails to interrupt the expression of a previously established one-trial morphine place preference [Review] KW - ibogaine KW - kappa opioid KW - mu opioid KW - Morphine KW - u50488 KW - spiradoline KW - Locomotor Activity KW - differential cross-tolerance KW - radioligand-binding KW - squirrel-monkey.rats.dopamine.mu.ibogaine KW - Agonists KW - Rats KW - ANTAGONIST KW - Kappa-Opioid KW - DRUGS KW - PREFERENCE KW - place preference KW - RECEPTOR AGONIST KW - Nucleus Accumbens KW - body temperature JO - Progress Neuropsychopharmacology & Biol Psych PY - 1996 AB - The selective kappa agonists U50488 (10 mg/kg, i.p.) and spiradoline (1 mg/kg, i.p.) attenuated the locomotor activating effects of a morphine challenge (5 mg/kg, i.p.) administered 19 h later in rats. This antagonism of morphine by a re agonist was reversed by the selective kappa antagonist, norbinaltorphimine (10 mg/kg, s.c.). Furthermore, the kappa opioid antagonism of morphine was enhanced by prior morphine exposure (2 doses of 30 mg/kg, i.p. administered once a day for 2 days). The present data suggest that kappa-mu opioid interactions may occur over time periods that exceed the acute durations of drug actions. [References: 36] RP - NOT IN FILE SP - 857 EP - 872 VL - 20 ER - TY - JOUR AU - Madinaveitia,A. AU - Reina,M. AU - Delafuente,G. AU - Gonzalez,A.G. AU - Valencia,E. TI - Obovamine, a New Indole Alkaloid from Stemmadenia Obovata KW - ibogaine KW - ANTIMICROBIALLY ACTIVE ALKALOIDS KW - TABERNAEMONTANA KW - STEREOCHEMISTRY KW - alkaloid KW - Indoles KW - indole alkaloid KW - Coronaridine JO - J NAT.PROD. PY - 1996 AB - The stem bark of the Panamanian plant Stemmademia obovata has afforded a new ibogaine-type alkaloid, obovamine (1), whose structure was determined by a combination of spectral interpretation and chemical correlations. Ten known alkaloids, coronaridine, coronaridine hydroxyindolenine, voacangine, voacangine hydroxyindolenine, (19S)-heyneanine, (19S)-heyneanine hydroxyindolenine, (19S)-voacristine, (19S)-voacristine hydroxyindolenine, ajmalicine, and ajmalicinine, were also isolated. Voacangine was the main alkaloid constituent RP - NOT IN FILE SP - 185 EP - 189 VL - 59 ER - TY - JOUR AU - Matwyshyn,G.A. AU - Bhargava,H.N. TI - Effect of Ibogaine on Morphine and U 50,488H Induced Analgesia and Hypothermia in the Mouse KW - ibogaine KW - Morphine KW - ANALGESIA KW - MOUSE JO - FASEB J PY - 1996 RP - NOT IN FILE SP - 2618 EP - 2618 VL - 10 ER - TY - JOUR AU - Onwere,I. AU - Chakrabarti,A. AU - Ali,S.F. AU - Onaivi,E.S. TI - Effect of Ibogaine on Cocaine Withdrawal Anxiogenesis in Mice KW - ibogaine KW - Cocaine KW - Mice KW - Withdrawal JO - FASEB J PY - 1996 RP - NOT IN FILE SP - 2595 EP - 2595 VL - 10 ER - TY - JOUR AU - Pearl,S.M. AU - Glick,S.D. TI - Prolonged antagonism of morphine-induced locomotor stimulation by kappa opioid agonists - enhancement by prior morphine exposure KW - ibogaine KW - Kappa-Opioid KW - Agonists KW - Morphine KW - kappa opioid JO - Neurosci Lett PY - 1996 RP - NOT IN FILE SP - 5 EP - 8 VL - 213 ER - TY - JOUR AU - Scallet,A.C. AU - Ye,X. AU - Rountree,R.L. AU - Schmued,L.C. AU - Ati,S.F. TI - Ibogaine, a Putative Treatment for Drug-Addiction - Neuropathology in Rats and Mice KW - ibogaine KW - Rats KW - Mice KW - Neurotoxicity KW - Pathology JO - Brain Pathol PY - 1996 RP - NOT IN FILE SP - 356 EP - 356 VL - 6 ER - TY - JOUR AU - Sershen,H. AU - Hashim,A. AU - Lajtha,A. TI - The Effect of Ibogaine on Sigma Receptor Mediated and NMDA Receptor Mediated Release of (H 3) Dopamine KW - ibogaine KW - NMDA Receptor KW - Sigma Receptor KW - Pentazocine KW - MK-801 KW - Dopamine Release KW - Striatum (Mouse) KW - INDUCED LOCOMOTOR STIMULATION KW - Dopamine KW - Neurons KW - Cocaine KW - Brain KW - Mice KW - Rats KW - Indoles KW - alkaloid KW - In Vitro KW - Agonists KW - RECEPTORS KW - RELEASE KW - indole alkaloid KW - DRUGS KW - Radioligand Binding KW - Kappa-Opioid KW - Sigma Receptors KW - SITES KW - RECEPTOR AGONIST KW - SYSTEM JO - Brain Res Bull PY - 1996 AB - The indole alkaloid ibogaine has been suggested to have potential for inhibiting dependency on stimulant drugs. Radioligand binding studies have suggested possible multisite actions of ibogaine: affinity at the kappa-opioid, NMDA, and sigma receptors, with effects on dopamine (DA) release. To further investigate the multiplicity of sites of action of ibogaine and the presynaptic regulation of the DA release, the effect of ibogaine on NMDA- and sigma-receptor-mediated efflux of [H-3]DA was measured in striatal tissue from C57BL/6By mice. Striatal tissue was incubated in vitro with [H-3]DA and the effect on DA release was measured. Both NMDA (25 mu M) and the sigma receptor agonist (+/-)-pentazocine (20 mu M) alone increased the efflux of DA. (+/-)-Pentazocine (100 nM) did not inhibit the NMDA-evoked release. MK-801 (5 mu M) completely inhibited the NMDA-evoked release and inhibited the (+/-)- pentazocine-evoked release by 49%. Ibogaine (10 mu M) itself increased the efflux of DA; at 1 mu M it was without effect. Ibogaine (1 mu M) inhibited the NMDA-evoked release of DA by 31% and inhibited the (+/-)-pentazocine-evoked release by 48%. In addition, the level of basal release of DA obtained after the NMDA- or (+/-)-pentazocine-evoked-release remained higher in the tissue exposed to ibogaine throughout. The results suggest that sigma receptors can regulate the release of DA, along with an action at the NMDA receptor. We previously reported action of ibogaine at the kappa-opioid site. The elevated basal release of DA in the presence of ibogaine after NMDA-or (+/-)-pentazocine- evoked release may reflect the ibogaine-induced removal of the tonically active kappa-opioid system that acts presynaptically to reduce dopamine release. The kappa-opioid system also appears to be inhibitory on both the NMDA and sigma receptors RP - NOT IN FILE SP - 63 EP - 67 VL - 40 ER - TY - JOUR AU - Sershen,H. AU - Hashim,A. AU - Lajtha,A. TI - Effect of Ibogaine on Cocaine Induced Efflux of (H 3) Dopamine and (H 3) Serotonin from Mouse Striatum KW - ibogaine KW - Cocaine KW - Serotonin KW - Dopamine KW - Kappa-Opioid KW - INDUCED LOCOMOTOR STIMULATION KW - DOPAMINE RELEASE INVIVO KW - OPIOID RECEPTOR AGONIST KW - HUMAN CEREBRAL-CORTEX KW - SEROTONIN RELEASE KW - H-3 SEROTONIN KW - Rats KW - Brain KW - Mice KW - MECHANISMS KW - Indoles KW - alkaloid KW - Binding Sites KW - In Vitro KW - Agonists KW - LOCOMOTOR-ACTIVITY KW - Striatum KW - MOUSE KW - indole alkaloid KW - SITES KW - SYSTEM KW - RELEASE KW - Locomotor Activity KW - PRETREATMENT KW - INDUCED INCREASE KW - kappa opioid KW - U 62066 KW - BEHAVIOR JO - Pharmacol Biochem Behav PY - 1996 AB - Ibogaine, an indole alkaloid with proposed antiaddictive properties, has structural similarity to serotonin and has been shown to have affinity to the kappa-opioid binding site. In addition to the dopamine system, the serotonin system is a major target for cocaine action and the opioid system can affect the serotonin system. Therefore, the present study examined the effect of ibogaine on cocaine-induced, electrically evoked efflux of [H-3]dopamine and [H-3]serotonin from striatal tissue incubated in vitro, and their modulation by the kappa-opioid system. Cocaine (10(-6) M) added in vitro increased the fractional efflux of both [H-3]dopamine (FRS(2)/FRS(1) = 2.42 +/- 0.36) and [H-3]serotonin (FRS(2)/FRS(1) = 1.31 +/- 0.06). Mice treated in vivo with ibogaine (40 mg/kg or 2 times 40 mg/kg, IP) and killed 2 or 18 h later still showed the cocaine-induced increase in [H-3]dopamine, but [H-3]serotonin efflux was not increased. The 5-HT1B agonist CGS-12066A (10(-6) M, added in vitro) increased [H-3]dopamine release, but did not alter cocaine- induced efflux of [H-3]dopamine. CGS-12066A did not affect [H- 3]serotonin release, but the cocaine-induced increase in [H- 3]serotonin was inhibited. CGS-12066A (1 mg/kg, SC) potentiated cocaine (25 mg/kg, SC)-induced locomotor activity. Ibogaine pretreatment reduced both the cocaine and the CGS- 12066A cocaine- induced increase in locomotor activity. The kappa- opioid agonist U-62066 (10(-6) M, added in vitro) reduced both [H-3]dopamine and [H-3]serotonin release. This inhibitory effect was blocked by in vivo administration of ibogaine. U-62066 did not alter cocaine- induced [H-3]dopamine efflux, but reduced cocaine-induced [H- 3]serotonin efflux. In striatal tissue from ibogaine-pretreated mice, U-62066 restored the cocaine-induced increase in [H- 3]serotonin release. U-62066 (1 mg/kg, SC) potentiated cocaine- induced behavior and maintained an increased locomotor activity after ibogaine treatment. The results suggest that ibogaine may block the cocaine-mediated effects on serotonergic transmission, that subsequently modulate dopamine release. The kappa-opioid modulation of serotonergic transmission is also involved RP - NOT IN FILE SP - 863 EP - 869 VL - 53 ER - TY - JOUR AU - Sershen,H. AU - Hashim,A. AU - Lajtha,A. TI - The Effect of Ibogaine on Sigma Receptor Mediated and NMDA Receptor Mediated Release of (H 3) Dopamine KW - ibogaine KW - Sigma Receptor KW - RECEPTORS KW - NMDA Receptor KW - Dopamine KW - RELEASE JO - J Neurochem PY - 1996 RP - NOT IN FILE SP - S59 EP - S59 VL - 66 ER - TY - JOUR AU - Alburges,M.E. AU - Foltz,R.L. AU - Moody,D.E. TI - Determination of ibogaine and 12-hydroxy-ibogamine in plasma by gas chromatography positive ion chemical ionization mass spectrometry KW - ibogaine KW - Drug Dependence KW - Opioid Withdrawal KW - Naloxone KW - Sodium Shift KW - RECEPTOR-BINDING KW - Mice KW - Indoles KW - indole alkaloid KW - alkaloid KW - DRUGS KW - BEHAVIOR KW - Morphine KW - ANALGESIA KW - Withdrawal KW - Rats KW - Opioid Receptor KW - RECEPTORS KW - Brain KW - kappa opioid KW - mu opioid KW - MOUSE KW - POTENT KW - Ligands KW - Analysis KW - SITES KW - Agonists KW - INHIBITION JO - J Anal Toxicol PY - 1995 AB - The naturally occurring indole alkaloid ibogaine is of interest because of its reported ability to block drug seeking behavior for extended periods. The compound also potentiates morphine- induced analgesia in mice and reduces certain naltrexone- precipitated withdrawal signs in morphine-dependent rats. Although these results might suggest ibogaine interaction with opioid receptors, previous receptor binding studies (Brain Res. 571:242-247, 1980) found that ibogaine had a K-i value of only 2 mu M for the kappa opioid receptor and was virtually inactive in blocking mu and delta receptor binding (K-i > 100 mu M). The present investigation of ibogaine interaction with the mu opioid receptor from mouse forebrain labeled with [H-3]-naloxone, however, yielded significantly more potent mu opioid K-i values. LIGAND analysis indicated that the data were best fit by a two site binding model, with K-i values of about 130 nM and 4 mu M, reflecting ibogaine recognition of different agonist affinity states of the receptor. Inclusion of 100 mM NaCl in the assay to induce the agonist low affinity state of the receptor, reduced ibogaine's inhibition of [H-3]-naloxone binding. These results suggest that ibogaine is an agonist at the mu opioid receptor with a K-i value of about 130 nM, potentially explaining ibogaine's antinociceptive effects as well as its reported reduction of opioid withdrawal symptoms and attenuation of drug seeking behavior. [References: 20] RP - NOT IN FILE SP - 381 EP - 386 VL - 19 ER - TY - JOUR AU - Ali,S.F. AU - Chetty,S.C. AU - Meng,X.M. AU - Newport,G.D. AU - Slikker,W. TI - A Single Injection of Ibogaine Produces Selective Neurochemical Changes in Mouse Brain KW - ibogaine KW - MOUSE KW - Brain JO - J Neurochem PY - 1995 RP - NOT IN FILE SP - S172 EP - S172 VL - 65 ER - TY - JOUR AU - Bowen,W.D. AU - Vilner,B.J. AU - Williams,W. AU - Bertha,C.M. AU - Kuehne,M.E. AU - Jacobson,A.E. TI - Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity KW - ibogaine KW - Animal KW - Brain KW - Metabolism KW - Guinea Pigs KW - Hallucinogens KW - Analogs & Derivatives KW - Ligands KW - Liver KW - Radioligand Assay KW - Rats KW - Receptors,sigma KW - Harmaline KW - RECEPTORS KW - Tabernanthine KW - Ibogamine KW - CONGENERS KW - SITES KW - METABOLITES JO - Eur J Pharmacol PY - 1995 AB - Ibogaine (12-methoxyibogamine) exhibited moderate affinity for sigma 2 sites (Ki = 201 nM) and low affinity for sigma 1 sites (Ki = 8554 nM), thus showing 43-fold selectivity for sigma 2 receptors. Tabernanthine (13-methoxyibogamine) and (+/-)- ibogamine had sigma 2 Ki = 194 nM and 137 nM, respectively. However, they showed 3- to 5-fold higher sigma 1 affinity compared to ibogaine, resulting in about 14-fold selectivity for sigma 2 sites over sigma 1. A potential ibogaine metabolite, O- des-methyl-ibogaine, had markedly reduced sigma 2 affinity relative to ibogaine (Ki = 5,226 nM) and also lacked significant affinity for sigma 1 sites. (+/-)-Coronaridine ((+/-)-18- carbomethoxyibogamine) and harmaline (1-methyl-7-methoxy-3,4- dihydro-beta-carboline) lacked significant affinity for either sigma subtype. Thus, sigma 2 receptors could play a role in the actions of ibogaine RP - NOT IN FILE SP - R1 EP - R3 VL - 279 ER - TY - JOUR AU - Codd,E.E. TI - High Affinity Ibogaine Binding to a Mu Opioid Agonist Site KW - ibogaine KW - Drug Dependence KW - Opioid Withdrawal KW - Naloxone KW - Sodium Shift KW - RECEPTOR-BINDING KW - OPIATE RECEPTORS KW - Brain KW - Rats KW - Withdrawal KW - SODIUM KW - Mice KW - Indoles KW - alkaloid KW - DRUGS KW - BEHAVIOR KW - Morphine KW - ANALGESIA KW - RECEPTORS KW - Kappa-Opioid KW - MOUSE KW - POTENT KW - Ligands KW - Analysis KW - SITES KW - Agonists KW - INHIBITION KW - HIGH-AFFINITY KW - mu opioid KW - indole alkaloid KW - Opioid Receptor KW - kappa opioid JO - Life Sci PY - 1995 AB - The naturally occurring indole alkaloid ibogaine is of interest because of its reported ability to block drug seeking behavior for extended periods. The compound also potentiates morphine- induced analgesia in mice and reduces certain naltrexone- precipitated withdrawal signs in morphine-dependent rats. Although these results might suggest ibogaine interaction with opioid receptors, previous receptor binding studies (Brain Res. 571:242-247, 1980) found that ibogaine had a K-i value of only 2 mu M for the kappa opioid receptor and was virtually inactive in blocking mu and delta receptor binding (K-i > 100 mu M). The present investigation of ibogaine interaction with the mu opioid receptor from mouse forebrain labeled with [H-3]- naloxone, however, yielded significantly more potent mu opioid K- i values. LIGAND analysis indicated that the data were best fit by a two site binding model, with K-i values of about 130 nM and 4 mu M, reflecting ibogaine recognition of different agonist affinity states of the receptor. Inclusion of 100 mM NaCl in the assay to induce the agonist low affinity state of the receptor, reduced ibogaine's inhibition of [H-3]-naloxone binding. These results suggest that ibogaine is an agonist at the mu opioid receptor with a K-i value of about 130 nM, potentially explaining ibogaine's antinociceptive effects as well as its reported reduction of opioid withdrawal symptoms and attenuation of drug seeking behavior RP - NOT IN FILE SP - PL315 EP - PL320 VL - 57 ER - TY - JOUR AU - Dworkin,S.I. AU - Gleeson,S. AU - Meloni,D. AU - Koves,T.R. AU - Martin,T.J. TI - Effects of Ibogaine on Responding Maintained by Food, Cocaine and Heroin Reinforcement in Rats KW - ibogaine KW - Cocaine KW - Heroin KW - Self-Administration KW - Scheduled-Controlled Behavior KW - Fixed Ratio KW - INDUCED LOCOMOTOR STIMULATION KW - INVIVO MICRODIALYSIS KW - MOTOR BEHAVIOR KW - Morphine KW - Mice KW - Amphetamine KW - Withdrawal KW - Indoles KW - alkaloid KW - DRUGS KW - Drug Abuse KW - Rats KW - Food KW - Reinforcement KW - Reinforcement Schedule KW - PRETREATMENT KW - Self Administration KW - indole alkaloid JO - Psychopharmacology PY - 1995 AB - The effects of ibogaine (40 and 80 mg/kg, IF), an indole alkaloid proposed for the treatment of drug abuse, were determined in three different groups of rats responding under an FR10 schedule of food, cocaine or heroin reinforcement. Ibogaine (80 mg/kg, IF) given 60 min before the start of the session resulted in a 97% decrease in the number of ratios completed under the food reinforcement schedule and resulted in a decrease in responding the following day. Neither 40 mg/kg ibogaine given 60 min prior to the session nor 80 mg/kg given 24 h before the session suppressed responding maintained by cocaine infusions (0.33 mg/infusion). Pretreatment with 80 mg/kg ibogaine either 60 or 90 min prior to the session suppressed cocaine self- administration on the day it was administered and the longer pretreatment continued to suppress responding for 48 h. Responding maintained by heroin (18 mu g/infusion) was the most sensitive to the effects of ibogaine. Both 40 and 80 mg/kg ibogaine resulted in an almost complete suppression of responding following a 60-min pretreatment period. Responding maintained by heroin returned to control levels the day following the administration of ibogaine RP - NOT IN FILE SP - 257 EP - 261 VL - 117 ER - TY - JOUR AU - Gallagher,C.A. AU - Hough,L.B. AU - Keefner,S.M. AU - Seyed-Mozaffari,A. AU - Archer,S. AU - Glick,S.D. TI - Identification and quantification of the indole alkaloid ibogaine in biological samples by gas chromatography-mass spectrometry KW - ibogaine KW - Indoles KW - alkaloid KW - Animal KW - Brain KW - Metabolism KW - Brain Chemistry KW - Drug Stability KW - Female KW - Heating KW - Analysis KW - Mass Fragmentography KW - Methods KW - Rats KW - Rats,Sprague-Dawley KW - Reference Standards KW - Sensitivity and Specificity KW - Support,Non-U.S.Gov't KW - Support,U.S.Gov't,P.H.S. KW - Trifluoroacetic Acid KW - Analogs & Derivatives KW - Pharmacokinetics KW - Human KW - DRUGS KW - HUMANS KW - indole alkaloid KW - ANALOGS JO - Biochem Pharmacol PY - 1995 AB - A sensitive and highly selective analytical chemical method for measuring the indole alkaloid ibogaine in biological samples has been developed. The method utilizes organic extraction, derivatization with trifluoroacetic anhydride, and detection by combined gas chromatography-mass spectrometry. The deuterated analog of ibogaine, O-[Cd3]-ibogaine, was synthesized and used as an internal standard for the method. Standard curves, constructed from variable amounts of ibogaine (50-400 ng) and a fixed amount of internal standard (250 ng) were linear. The method has an approximate detection limit of at least 20 ng/mL of tissue extract (180 ng/g tissue), with a coefficient of variation of 8 to 12.5%. Chemical stability studies with the method found that aqueous ibogaine solutions (1-10 mg/mL) could be stored at 10 degrees for up to 7 months with no more than 10% loss. The method was also used to measure brain ibogaine levels in rats 1 and 19 hr after a single dose of drug (40 mg/kg, i.p.); the results suggest a rapid disappearance of the drug after i.p. dosing. The method will help reveal the pharmacokinetic properties of this putative anti-addictive agent in animals and humans RP - NOT IN FILE SP - 73 EP - 79 VL - 49 ER - TY - JOUR AU - Hearn,W.L. AU - Pablo,J. AU - Hime,G.W. AU - Mash,D.C. TI - Identification and Quantitation of Ibogaine and an O Demethylated Metabolite in Brain and Biological Fluids Using Gas Chromatography Mass Spectrometry KW - ibogaine KW - Rats KW - Brain KW - METABOLITES JO - J Anal Toxicol PY - 1995 RP - NOT IN FILE SP - 427 EP - 434 VL - 19 ER - TY - JOUR AU - House,R.V. AU - Thomas,P.T. AU - Bhargava,H.N. TI - Comparison of the hallucinogenic indole alkaloids ibogaine and harmaline for potential immunomodulatory activity KW - ibogaine KW - Indoles KW - alkaloid KW - Harmaline KW - Adjuvants,Immunologic KW - Pharmacology KW - Animal KW - B-Lymphocytes KW - drug effect KW - Comparative Study KW - Female KW - Hallucinogens KW - In Vitro KW - Interleukin-6 KW - Biosynthesis KW - Killer Cells,Natural KW - Macrophages KW - Secretion KW - Mice KW - Support,U.S.Gov't,P.H.S. KW - T-Lymphocytes KW - indole alkaloid JO - Pharmacology PY - 1995 AB - The immunomodulatory potential of the indole alkaloids ibogaine and harmaline was examined in a panel of in vitro immune function assays. These assays were chosen to assess T-cell regulatory and effector function, B-cell function, macrophage function, and natural killer-cell function. The in vitro exposure to either ibogaine or harmaline resulted in a dose-related suppression of all immune functions examined except macrophage function. This suppression was noted at various concentrations in different assays, but was generally only associated with high concentrations (10-100 mumol/l) RP - NOT IN FILE SP - 56 EP - 65 VL - 51 ER - TY - JOUR AU - Kesner,R.P. AU - Jacksonsmith,P. AU - Henry,C. AU - Amann,K. TI - Effects of Ibogaine on Sensory Motor Function, Activity, and Spatial Learning in Rats KW - ibogaine KW - Sensory-Motor Function KW - Spatial Learning KW - Morphine KW - Withdrawal KW - Water Maze KW - Hippocampus KW - DISSOCIATION KW - MEMORY KW - CORTEX KW - alkaloid KW - LONG-EVANS RAT KW - Rats KW - Reflex KW - Locomotor Activity KW - Motor Activity KW - Animal KW - learning JO - Pharmacol Biochem Behav PY - 1995 AB - Ibogaine, a naturally occurring alkaloid, has been show to reduce naloxone-precipitated withdrawal symptoms from morphine. Given the clinical possibilities, it is important to determine ibogaine's effects on sensory-motor function, activity, learning, and memory. Long-Evans rats injected with doses of 20- 60 mg/kg of ibogaine displayed slower response times on sensory and sensory-motor tests and were impaired in performing specific motor reflexes at doses of 40-60 mg/kg. Furthermore, these rats showed a marked reduction in locomotor and nonlocomotor activity, as well as emotionality at doses ranging from 10-40 mg/kg. At the higher doses the rats appeared to be virtually inactive. There were also deficits in learning a spatial location task (a dry- land version of the Morris water-maze). The deficits, however, were probably due to a reduction in locomotor activity and reduction in detection of sensory information. In a final experiment, a single injection of 40 mg/kg of ibogaine had marked deleterious effects on the acquisition of the spatial location task 1 but not 7 days after the injection, even though in this case there were no effects on sensory motor function 1 or 7 days after the injection. Thus, there are severe sensory- motor activity and learning problems while the animal is under the influence of ibogaine (acute effect) as well as long-term consequences on learning without concomitant changes in sensory- motor function RP - NOT IN FILE SP - 103 EP - 109 VL - 51 ER - TY - JOUR AU - Mach,R.H. AU - Smith,C.R. AU - Childers,S.R. TI - Ibogaine Possesses a Selective Affinity for Sigma(2) Receptors KW - ibogaine KW - Sigma Receptors KW - Substance Abuse KW - INDUCED LOCOMOTOR STIMULATION KW - PARASAGITTAL ZONES KW - Cocaine KW - Rats KW - Dopamine KW - Brain KW - SUPERSENSITIVITY KW - METABOLITES KW - Amphetamine KW - Cerebellum KW - alkaloid KW - DRUGS KW - MECHANISMS KW - In Vitro KW - Sigma Receptor KW - RECEPTORS KW - HIGH-AFFINITY KW - Structure-Activity Relationship KW - Ligands KW - craving JO - Life Sci PY - 1995 AB - The alkaloid ibogaine is potentially useful to reduce craving for several drugs of abuse, but its mechanism of action is not known. In the current study, in vitro studies were conducted in order to determine the affinity of ibogaine for sigma receptors. Our results indicate that ibogaine has a relatively high affinity for sigma(2) receptors (K-i = 90.4 and 250 nM) and a significantly lower affinity for sigma(1) receptors (K-i = 9310 nM). These data suggest that ibogaine may have a higher affinity at sigma(2) receptors than any other known CNS receptor. Its low affinity for sigma(1) receptors also suggests that ibogaine may be a suitable lead compound for structure-activity relationship studies aimed at developing sigma(2)-selective ligands RP - NOT IN FILE SP - PL57 EP - PL62 VL - 57 ER - TY - JOUR AU - Mash,D.C. AU - Staley,J.K. AU - Pablo,J.P. AU - Holohean,A.M. AU - Hackman,J.C. AU - Davidoff,R.A. TI - Properties of Ibogaine and Its Principal Metabolite (12 Hydroxyibogamine) at the mK 801 Binding Site of the NMDA Receptor Complex KW - ibogaine KW - Hydroxyibogamine KW - MK-801 KW - N-Methyl-D-Aspartate Receptors KW - Spinal Cord KW - Caudate KW - Cerebellum KW - Drug Abuse KW - TOLERANCE KW - BLOCKADE KW - Cocaine KW - Rats KW - ANTAGONIST KW - ETHANOL KW - alkaloid KW - Binding Sites KW - RECEPTORS KW - Human KW - POTENT KW - NMDA Receptor KW - BEHAVIOR KW - RECEPTOR COMPLEX KW - COMPLEX KW - METABOLITES KW - 12-Hydroxyibogamine KW - SITES JO - Neurosci Lett PY - 1995 AB - The putative anti-addiction alkaloid ibogaine and its principal metabolite 12-hydroxyibogamine appear to act at the (+)-5 methyl- 10,11-dihydro-5H-dibenzo[a,d]cycloheten-5-10 maleate (MK-801) binding site in the N-methyl-D-aspartate (NMDA)- receptor cation channel. This conclusion is based on findings that both compounds competitively displaced specific [H-3]MK-801 binding to membranes from postmortem human caudate and cerebellum and from frog spinal cord. Ibogaine was 4-6-fold more potent than its metabolite and both compounds were less potent (50-1000-fold) than MK-801 binding to the NMDA receptor. In addition, ibogaine (100 mu M) and 12-hydroxyibogamine (1 mM) blocked (85-90% of control) the ability of NMDA (100 mu M, 5 s) to depolarize frog motoneurons in the isolated frog spinal cord. The prevention of NMDA- depolarizations in frog motoneurons showed use-dependency and was very similar to the block produced by MK-801. In view of the abilities of MK-801 to affect the responses to addictive substances in pre-clinical investigations, our results are compatible with the idea that the ability of ibogaine and 12- hydroxyibogamine to interrupt drug-seeking behavior may, in part, result from their actions at the MK-801 binding site RP - NOT IN FILE SP - 53 EP - 56 VL - 192 ER - TY - JOUR AU - Mash,D.C. AU - Staley,J.K. AU - Baumann,M.H. AU - Rothman,R.B. AU - Hearn,W.L. TI - Identification of a Primary Metabolite of Ibogaine That Targets Serotonin Transporters and Elevates Serotonin KW - ibogaine KW - 12-Hydroxyibogamine KW - Serotonin Transporters KW - Microdialysis KW - Desmethyl Ibogaine KW - Rats KW - Indoles KW - Cocaine KW - METABOLITES KW - DRUGS KW - Hydroxyibogamine KW - HIGH-AFFINITY KW - Radioligand Binding KW - POTENT KW - Dopamine KW - Nucleus Accumbens KW - BEHAVIOR KW - HUMANS KW - Serotonin KW - craving JO - Life Sci PY - 1995 AB - Ibogaine is a hallucinogenic indole with putative efficacy for the treatment of cocaine, stimulant and opiate abuse. The purported efficacy of ibogaine following single dose administrations has led to the suggestion that a long-acting metabolite of ibogaine may explain in part how the drug reduces craving for psychostimulants and opiates. We report here that 12- hydroxyibogamine, a primary metabolite of ibogaine, displays high affinity for the 5-HT transporter and elevates extracellular 5- HT. In radioligand binding assays, 12- hydroxyibogamine was 50- fold more potent at displacing radioligand binding at the 5-HT transporter than at the DA transporter. Ibogaine and 12- hydroxyibogamine were equipotent at the dopamine transporter. In vivo microdialysis was used to evaluate the acute actions of ibogaine and 12-hydroxyibogamine on the levels of DA and 5-HT. Administration of 12- hydroxyibogamine produced a marked dose- related elevation of extracellular 5-HT. Ibogaine and 12- hydroxyibogamine failed to elevate DA levels in the nucleus accumbens over the dose range tested. The elevation in synaptic levels of 5-HT by 12- hydroxyibogamine may heighten mood and attenuate drug craving. The effects of the active metabolite on 5- HT transmission may account in part for the potential of ibogaine to interrupt drug- seeking behavior in humans RP - NOT IN FILE SP - PL45 EP - PL50 VL - 57 ER - TY - JOUR AU - Mash,D.C. AU - Douyon,R. AU - Hearn,W.L. AU - Sambol,N.C. AU - Sanchezramos,J. TI - A Preliminary Report on the Safety and Pharmacokinetics of Ibogaine KW - ibogaine KW - Pharmacokinetics JO - Biol Psychiat PY - 1995 RP - NOT IN FILE SP - 652 EP - 652 VL - 37 ER - TY - JOUR AU - O'Hearn,E. AU - Zhang,P. AU - Molliver,M.E. TI - Excitotoxic Insult Due to Ibogaine Leads to Delayed Induction of Neuronal Nos in Purkinje Cells KW - ibogaine KW - NADPH-Diaphorase KW - Nitric Oxide Synthase (Nos) KW - Purkinje Cell KW - Cerebellum KW - Excitotoxicity KW - Neurotoxicity KW - Microglia KW - Hallucinogen KW - Addiction KW - Nitric-Oxide Synthase KW - PARASAGITTAL ZONES KW - RAT-BRAIN KW - MESSENGER KW - AXOTOMY KW - Neurons KW - RELEASE KW - Purkinje Cells KW - Recovery KW - Cell Death JO - Neuroreport PY - 1995 AB - IBOGAINE causes degeneration of Purkinje cells (PKCs), presumably via activation of neurons in the inferior olive leading to release of glutamate at climbing fiber terminals. Following ibogaine administration, some Purkinje cells express NADPH-diaphorase and neuronal NOS (nNOS), neither of which is present normally in these cells. The induction of NOS is delayed in onset, dose-related, and detected in neurons adjacent to degenerated PKCs. The results demonstrate that nNOS induction can follow excitotoxic neuronal injury or perturbation. However, NO is unlikely to participate in the initial phase of PKC damage. Both the late induction of nNOS and the spatial relationship between damaged and nNOS-expressing PKCs are consistent with a role for NO in either neuronal recovery or delayed cell death following excitotoxic injury RP - NOT IN FILE SP - 1611 EP - 1616 VL - 6 ER - TY - JOUR AU - Pearl,S.M. AU - Johnson,D.W. AU - Glick,S.D. TI - Prior Morphine Exposure Enhances Ibogaine Antagonism of Morphine Induced Locomotor Stimulation KW - ibogaine KW - Morphine KW - Locomotor Activity KW - INVIVO MICRODIALYSIS KW - NUCLEUS-ACCUMBENS KW - Dopamine Release KW - Rats KW - PRETREATMENT KW - Amphetamine KW - ANALGESIA KW - Mice KW - BEHAVIOR KW - Naloxone KW - Female KW - LOCOMOTOR-ACTIVITY KW - Addiction KW - INDUCED LOCOMOTOR STIMULATION JO - Psychopharmacology PY - 1995 AB - Ibogaine is currently being investigated for its potential use as an anti-addictive agent. In the present study we sought to determine whether prior morphine exposure influences the ability of ibogaine to inhibit morphine-induced locomotor stimulation. Female Sprague-Dawley rats were pretreated once a day for 1-4 days with morphine (5, 10, 20 or 30 mg/kg, IF) or saline and then received ibogaine (40 mg/kg, IF) 5 h after the last morphine pretreatment dose. Compared to rats pretreated with saline, rats pretreated with morphine (10, 20 or 30 mg/kg, IF) before ibogaine (40 mg/kg, IF) showed a significant reduction in morphine-induced (5 mg/kg, IF) locomotor stimulation when tested 19 h after ibogaine administration. Furthermore, this effect was apparent over a range of ibogaine (5-60 mg/kg, IF) and morphine test (2.5- 5 mg/kg, IF) dosages. Doses of ibogaine (5 and 10 mg/kg, IF) which alone were inactive inhibited morphine-induced locomotor activity when rats had been pretreated with morphine. These results, showing that morphine pre-exposure affects ibogaine activity, suggest that variable histories of opioid exposure might account for individual differences in the efficacy of ibogaine to inhibit opioid addiction RP - NOT IN FILE SP - 470 EP - 475 VL - 121 ER - TY - JOUR AU - Pearl,S.M. AU - Herrickdavis,K. AU - Teitler,M. AU - Glick,S.D. TI - Radioligand Binding Study of Noribogaine, a Likely Metabolite of Ibogaine KW - ibogaine KW - Noribogaine KW - Desmethyl Ibogaine KW - Opioid Receptor KW - INVIVO MICRODIALYSIS KW - LOCOMOTOR-ACTIVITY KW - Rats KW - Morphine KW - SYSTEM KW - Radioligand Binding KW - METABOLITES KW - RECEPTORS KW - Kappa-Opioid KW - radioligand-binding KW - kappa opioid JO - Brain Res PY - 1995 AB - Radioligand-binding studies were performed to ascertain the actions of noribogaine, a suspected metabolite of ibogaine, on opioid receptors. Consistent with previous results, ibogaine showed highest affinity for kappa opioid receptors (K-i = 3.77 +/- 0.81 mu M), less affinity for mu receptors (K-i = 11.04 +/- 0.66 mu M) and no affinity for delta receptors (K-i > 100 mu M). Noribogaine showed a higher affinity than ibogaine for all of the opioid receptors: kappa K-i = 0.96 +/- 0.08 mu M, mu K-i- = 2.66 +/- 0.62 mu M and delta K-i = 24.72 +/- 2.26 mu M. These data suggest that noribogaine is active in vivo and that it may contribute to ibogaine's pharmacological effects RP - NOT IN FILE SP - 342 EP - 344 VL - 675 ER - TY - JOUR AU - Popik,P. AU - Layer,R.T. AU - Fossom,L.H. AU - Benveniste,M. AU - Geterdouglass,B. AU - Witkin,J.M. AU - Skolnick,P. TI - NMDA Antagonist Properties of the Putative Antiaddictive Drug, Ibogaine KW - ibogaine KW - INDUCED LOCOMOTOR STIMULATION KW - MORPHINE-TOLERANCE KW - RECEPTOR COMPLEX KW - BEHAVIORAL SENSITIZATION KW - PARASAGITTAL ZONES KW - RAPID TOLERANCE KW - Binding Sites KW - D-SERINE KW - MK-801 KW - Mice KW - HUMANS KW - Addiction KW - Nicotine KW - ANTAGONIST KW - RECEPTORS KW - RAT KW - Naloxone KW - Glycine KW - alkaloid KW - Morphine KW - Morphine Dependence KW - DRUGS KW - NMDA Receptor KW - Cell Death KW - BEHAVIOR KW - discriminative stimulus KW - dizocilpine KW - PRETREATMENT JO - J Pharmacol Exp Ther PY - 1995 AB - Both anecdotal reports in humans and preclinical studies indicate that ibogaine interrupts addiction to a variety of abused substances including alcohol, opiates, nicotine and stimulants. Based on the similarity of these therapeutic claims to recent preclinical studies demonstrating that N-methyl-D- aspartate (NMDA) antagonists attenuate addiction-related phenomena, we examined the NMDA antagonist properties of ibogaine. Pharmacologically relevant concentrations of ibogaine produce a voltage-dependent block of NMDA receptors in hippocampal cultures (K-i, 2.3 mu M at -60 mV). Consistent with this observation, ibogaine competitively inhibits [H-3]1-[1-(2- thienyl)-cyclohexyl]piperidine binding to rat forebrain homogenates (K-i, 1.5 mu M) and blocks glutamate-induced cell death in neuronal cultures (IC50, 4.5 mu M). Moreover, at doses previously reported to interfere with drug-seeking behaviors, ibogaine substitutes as a discriminative stimulus (ED(50), 64.9 mg/kg) in mice trained to discriminate the prototypic voltage- dependent NMDA antagonist, dizocilpine (0.17 mg/kg), from saline. Consistent with previous reports, ibogaine reduced naloxone- precipitated jumping in morphine-dependent mice (ED(50), 72 mg/kg). Although pretreatment with glycine did not affect naloxone-precipitated jumping in morphine-dependent mice, it abolished the ability of ibogaine to block naloxone- precipitated jumping. Taken together, these findings link the NMDA antagonist actions of ibogaine to a putative ''antiaddictive'' property of this alkaloid, its ability to reduce the expression of morphine dependence RP - NOT IN FILE SP - 753 EP - 760 VL - 275 ER - TY - JOUR AU - Popik,P. AU - Layer,R.T. AU - Skolnick,P. TI - 100 years of ibogaine: neurochemical and pharmacological actions of a putative anti-addictive drug. [Review] KW - ibogaine KW - Adjuvants,Immunologic KW - pd [pharmacology] KW - Animal KW - B-Lymphocytes KW - drug effect KW - Comparative Study KW - Female KW - Hallucinogens KW - Harmaline KW - In Vitro KW - Interleukin-6 KW - Biosynthesis KW - Killer Cells,Natural KW - Macrophages KW - se [secretion] KW - Mice KW - Support,U.S.Gov't,P.H.S. KW - T-Lymphocytes KW - Indoles KW - indole alkaloid KW - alkaloid KW - DRUGS JO - Pharmacol Rev PY - 1995 AB - The immunomodulatory potential of the indole alkaloids ibogaine and harmaline was examined in a panel of in vitro immune function assays. These assays were chosen to assess T-cell regulatory and effector function, B-cell function, macrophage function, and natural killer-cell function. The in vitro exposure to either ibogaine or harmaline resulted in a dose-related suppression of all immune functions examined except macrophage function. This suppression was noted at various concentrations in different assays, but was generally only associated with high concentrations (10-100 mumol/l) RP - NOT IN FILE SP - 235 EP - 253 VL - 47 ER - TY - JOUR AU - Rezvani,A.H. AU - Overstreet,D.H. AU - Leef,Y.W. TI - Attenuation of Alcohol Intake by Ibogaine in 3 Strains of Alcohol Preferring Rats KW - ibogaine KW - Fawn-Hooded Rats KW - Alcohol-Preferring Rats KW - Alcohol Drinking KW - Blood Alcohol KW - Alcohol Seeking Behavior KW - Herbal Medicine KW - Alternative Medicine KW - NUCLEUS-ACCUMBENS KW - D-AMPHETAMINE KW - STIMULATED CONTRACTIONS KW - INVIVO MICRODIALYSIS KW - LOCOMOTOR-ACTIVITY KW - ETHANOL KW - Dopamine KW - Drinking KW - PREFERENCE KW - Morphine KW - Rats KW - Blood KW - TOLERANCE KW - Food KW - INVOLVEMENT JO - Pharmacol Biochem Behav PY - 1995 AB - Alcohol-preferring (P), Fawn-Hooded (FH) and alcohol- accepting (AA) rats were injected intraperitoneally (IP) or subcutaneously (SC) with different doses (10, 30, and 60 mg/kg) of Ibogaine or vehicle. In a separate experiment, FH rats were administered intragastrically (IG) with either 60 mg/kg of Ibogaine or vehicle for 5 days. In addition, the effects of Ibogaine on blood alcohol concentrations were measured. Our data show that, contrary to the SC administration of Ibogaine, IP administration of the agent significantly and dose-dependently reduced alcohol intake in these rats. Subchronic IG administration of 60 mg/kg of Ibogaine into FH rats significantly reduced alcohol intake without the development of tolerance or a significant effect on food or water intake. A single IP injection of 60 mg/kg Ibogaine into FH rats did not affect the blood alcohol levels. These results show that Ibogaine when injected IP or IG, but not SC, can significantly reduce alcohol intake without an effect on blood alcohol concentrations or food intake. These findings may suggest the involvement of Ibogaine's metabolite(s) in reducing alcohol intake. Although the neuronal mechanism(s) of action of Ibogaine on the regulation of alcohol intake is not fully understood, it is speculated that Ibogaine or its metabolite(s) exerts its attenuating effect on alcohol intake by modulating neurotransmitters/neuromodulators proposed to be involved in regulation of alcohol consumption RP - NOT IN FILE SP - 615 EP - 620 VL - 52 ER - TY - JOUR AU - Sershen,H. AU - Hashim,A. AU - Lajtha,A. TI - The Effect of Ibogaine on Kappa Opioid Induced and 5 HT3 Induced Changes in Stimulation Evoked Dopamine Release in Vitro from Striatum of C57BL/6By Mice KW - ibogaine KW - Kappa-Opioid Receptor KW - U 62066 KW - HT3 KW - Phenylbiguanide KW - Dopamine KW - Cocaine KW - 5-HT3 RECEPTOR ANTAGONISTS KW - COCAINE-INDUCED LOCOMOTION KW - PHARMACOLOGICAL CHARACTERIZATION KW - H-3 DOPAMINE KW - UPTAKE SITES KW - RAT KW - INVIVO KW - Microdialysis KW - INVOLVEMENT KW - CONGENERS KW - Indoles KW - alkaloid KW - DRUGS KW - Kappa-Opioid KW - Serotonin KW - Agonists KW - In Vitro KW - Tritium KW - Mice KW - Animal KW - RELEASE KW - PRETREATMENT KW - RECEPTORS KW - Dopamine Release KW - Striatum KW - kappa opioid KW - indole alkaloid KW - SYSTEM JO - Brain Res Bull PY - 1995 AB - Ibogaine is an indole alkaloid that has been suggested to have potential efficacy for interrupting dependency on stimulant drugs. The kappa-opioid and serotonin 5-HT3 systems may be involved in the action of ibogaine, related to their modulation of dopaminergic transmission. The kappa-opioid agonist U 62066 attenuated the in vitro stimulation-evoked efflux of tritium label from striatal tissue prelabeled with [H-3]dopamine. In mice pretreated with ibogaine . HCI (40 mg/kg IP given 2 h prior or 2 x 40 mg/kg and animals killed 18 h later), the inhibitory effect of U 62066 on stimulation-evoked release of tritium was eliminated, The 5-HT3 agonist phenylbiguanide had a biphasic effect on stimulation-evoked release of tritium; at 10(-6) M phenylbiguanide, stimulation-evoked release was attenuated. At 10(-5) M the basal outflow of tritium was increased. Ibogaine pretreatment had no effect on basal or stimulation-evoked release in the presence of 10(-6) M phenylbiguanide, but increased the stimulation-evoked outflow of tritium in the presence of 10(-5) M phenylbiguanide. Cocaine (10(-6) M), a dopamine uptake blocker, increased the electrically-evoked release of dopamine; ibogaine pretreatment did not affect the enhanced electrically-induced release of [H-3]dopamine by in vitro cocaine. The effects of ibogaine on the kappa-opioid and 5- HT3 receptors, located presynaptically on striatal dopamine terminals, modulating dopamine release may partly underlie its putative antiaddictive properties RP - NOT IN FILE SP - 587 EP - 591 VL - 36 ER - TY - JOUR AU - Shen,T.Y. TI - Medicinal Chemical Studies of Antiinflammatory and Analgesic Natural Products KW - ibogaine KW - Natural Products KW - Antiinflammatory and Analgesic Agents KW - Arachidonic Acid Cascade KW - Cyclooxygenase Inhibitors KW - Lipoxygenase Inhibitors KW - Platelet Activating Factor Antagonists KW - Dual Functional Inhibitors KW - Neolignan KW - Epibatidine KW - Acetylcholine Nicotinic Receptor Agonist KW - Antiaddictive Effects KW - PLATELET-ACTIVATING-FACTOR KW - RECEPTOR ANTAGONIST KW - ANALOGS KW - INHIBITION KW - POTENT KW - Analgesics KW - Biosynthesis KW - RECEPTORS KW - ANTAGONIST KW - alkaloid KW - Agonists KW - DRUGS KW - RECEPTOR AGONIST JO - J Chin Chem Soc PY - 1995 AB - Following the discovery of salicylates and its conversion to aspirin, natural products research has provided many promising leads for further modification as anti-inflammatory and analgesic agents. Recent studies have focused on biosynthesis inhibitors of eicosanoids and receptor antagonists of the platelet activating factor, including a new class of dual functional inhibitors derived from neolignans. The highly potent analgesic alkaloid epibatidine from the frog skin has been synthesized and recharacterized as a very strong acetylcholine nicotinic receptor agonist. Some novel epibatidine analogs have shown promise as potential CNS drugs and research probes for clarifying the anti- addictive property of the African alkaloid ibogaine RP - NOT IN FILE SP - 617 EP - 621 VL - 42 ER - TY - JOUR AU - Sweetnam,P.M. AU - Lancaster,J. AU - Snowman,A. AU - Collins,J.L. AU - Perschke,S. AU - Bauer,C. AU - Ferkany,J. TI - Receptor Binding Profile Suggests Multiple Mechanisms of Action Are Responsible for Ibogaines Putative Anti Addictive Activity KW - ibogaine KW - Drug Abuse KW - Addiction KW - Neurotransmitter Receptors KW - Radioligand Binding KW - RAT-BRAIN KW - PARASAGITTAL ZONES KW - SELECTIVE LIGAND KW - NERVOUS-SYSTEM KW - HIGH-AFFINITY KW - Cocaine KW - Morphine KW - SITES KW - ANTAGONIST KW - ONDANSETRON KW - Indoles KW - alkaloid KW - MECHANISMS KW - RECEPTORS KW - Ion Channels KW - MESSENGER KW - In Vitro KW - Dopamine KW - Serotonin KW - UPTAKE SITES KW - INHIBITION KW - RECEPTOR-BINDING KW - indole alkaloid KW - SYSTEM KW - SODIUM JO - Psychopharmacology PY - 1995 AB - The indole alkaloid ibogaine (NIH 10567, Endabuse) is currently being examined for its potential utility in the treatment of cocaine and opioid addiction. However, a clearly defined molecular mechanism of action for ibogaine's putative anti- addictive properties has not been delineated. Radioligand binding assays targeting over 50 distinct neurotransmitter receptors, ion channels, and select second messenger systems were employed to establish a broad in vitro pharmacological profile for ibogaine. These studies revealed that ibogaine interacted with a wide variety of receptors at concentrations of 1-100 mu M. These included the mu, delta, kappa, opiate, 5HT(2), 5HT(3), and muscarinic(1 and 2) receptors, and the dopamine, norepinephrine, and serotonin uptake sites. In addition, ibogaine interacted with N-methyl-D-aspartic acid (NMDA) associated ion and sodium ion channels as determined by the inhibition of [H-3]MK-801 and [H- 3]bactrachotoxin A 20-alpha- benzoate binding (BTX-B), respectively. This broad spectrum of activity may in part be responsible for ibogaine's putative anti- addictive activity RP - NOT IN FILE SP - 369 EP - 376 VL - 118 ER - TY - JOUR AU - Touchette,N. TI - Anti Addiction Drug Ibogaine on Trial KW - ibogaine KW - Addiction KW - DRUGS JO - Nature Med PY - 1995 RP - NOT IN FILE SP - 288 EP - 289 VL - 1 ER - TY - JOUR AU - Witkin,J.M. AU - Brave,S. AU - French,D. AU - Geterdouglass,B. TI - Discriminative Stimulus Effects of R (+) 3 Amino 1 Hydroxypyrrolid 2 One, ((+) Ha 966), a Partial Agonist of the Strychnine Insensitive Modulatory Site of the N Methyl D Aspartate Receptor KW - ibogaine KW - NMDA Receptor KW - D-CYCLOSERINE KW - GLYCINE RECEPTOR KW - CHLOROKYNURENIC ACID KW - EXHIBIT ANTIDEPRESSANT KW - XENOPUS OOCYTES KW - ANTAGONIST KW - Convulsions KW - COMPLEX KW - HA-966 KW - Glycine KW - RECEPTORS KW - Agonists KW - Male KW - Mice KW - Food KW - Ion Channels KW - Strychnine KW - discriminative stimulus KW - SITES KW - RECEPTOR COMPLEX KW - BEHAVIOR KW - dizocilpine KW - ifenprodil JO - J Pharmacol Exp Ther PY - 1995 AB - The strychnine-insensitive glycine site on the N-methyl-D- aspartate (NMDA) receptor complex is a target for development of a host of therapeutic agents including anxiolytics, antidepressants, antiepileptics, anti-ischemics and cognitive enhancers. In the present experiments, the discriminative stimulus effects of (+)-HA-966 [R-(+)-5-amino-1-hydroxypyrrolid- 2-one], a low-efficacy partial agonist of the glycine site, was explored. Male, Swiss-Webster mice were trained to discriminate (+)-HA-966 (170 mg/kg i.p.) from saline in a T-maze under which behavior was controlled by food. Other glycine partial agonists, 1-amino-1-cyclopropanecarboxilic acid and D-cycloserine, fully substituted for the discriminative stimulus effects of (+)-HA- 966 despite known differences in other pharmacological effects of these compounds. The glycine site antagonist, 7- chlorkynurenic acid, did not substitute for (+)-HA-966. Likewise other functional NMDA antagonists acting at nonglycine sites of the NMDA receptor also did not substitute: neither the high (dizocilpine) or low affinity (ibogaine) ion-channel blocker, the competitive antagonist, NPC 17742 [2R,4R,5S-2-amino-4,5-(1,2- cyclohexyl)-7-phosphonoheptanoic acid], nor the polyamine antagonist, ifenprodil, substituted for (+)-HA-966. Although the full agonist, glycine, did riot substitute, this compound fully blocked the discriminative stimulus effects of (+)-HA-966. In a separate group of mice trained to discriminate 0.17 mg/kg of dizocilpine from saline, (+)-HA-966 produced a maximum of only 50% dizocilpine-appropriate responses. These data suggest that the discriminative stimulus effects of (+)-HA-966 are based upon its partial agonist actions at the strychnine-insensitive glycine site. Furthermore, the lack of substitution of compounds with phencyclidine-like effects (dizocilpine, ibogaine and NPC 17742) or sedative properties (NPC 17742 and (-)-HA-966) suggests that these side-effects may not be part of the subjective effect profile of glycine partial agonists RP - NOT IN FILE SP - 1267 EP - 1273 VL - 275 ER - TY - JOUR AU - Broderick,P.A. AU - Phelan,F.T. AU - Eng,F. AU - Wechsler,R.T. TI - Ibogaine modulates cocaine responses which are altered due to environmental habituation: in vivo microvoltammetric and behavioral studies KW - ibogaine KW - Cocaine KW - Animal KW - Anxiety KW - Psychology KW - Behavior,Animal KW - drug effect KW - Pharmacology KW - Dopamine KW - Metabolism KW - Electrochemistry KW - Environment KW - Habituation KW - Psychophysiology KW - Male KW - Microelectrodes KW - Motor Activity KW - Nucleus Accumbens KW - Anatomy & Histology KW - Rats KW - Rats,Sprague-Dawley KW - Serotonin KW - Stereotyped Behavior KW - Support,Non-U.S.Gov't KW - Support,U.S.Gov't,P.H.S. KW - Indoles KW - alkaloid KW - Grooming KW - LOCOMOTOR-ACTIVITY KW - RELEASE KW - BEHAVIORAL-RESPONSE KW - indole alkaloid KW - BEHAVIOR KW - Locomotor Activity JO - Pharmacol Biochem Behav PY - 1994 AB - Ibogaine, a serotonergic (5-HTergic) indole alkaloid, was studied for cocaine modulatory effects on four parameters of behavior by computerized infrared photocell beam detection. The behavioral parameters were: a) locomotor activity (ambulations), b) rearing, c) stereotypy (fine movements, primarily grooming), and d) agoraphobia [(thigmotaxis) a natural tendency to avoid the center of the behavioral chamber]. With each behavioral data point, dopamine (DA) release, and serotonin (5-HT) release were detected within seconds in nucleus accumbens (NAcc) of the same behaving male Sprague-Dawley rats, using in vivo electrochemistry (voltammetry). Ibogaine was administered (40 mg/kg IP) for 4 consecutive days. Importantly, the DAergic and the 5-HTergic responses to (SC) cocaine and two behavioral responses, ambulations and central ambulations, were reduced in intensity due to extended time spent in the novel behavioral chamber (habituated). Rearing and fine movement patterns were not habituated. The results show that ibogaine downmodulated the (SC) cocaine-induced increase in NAcc DA release (p < 0.0001) and potentiated the (SC) cocaine-induced decrease in NAcc 5-HT release (p < 0.0001). Concurrently, ibogaine downmodulated cocaine-induced ambulation (p < 0.0001) and central ambulation behavior (p < 0.0001). On the other hand, the behavioral parameters that did not exhibit habituation, i.e., rearing behavior and fine movement behavior, were not downmodulated by ibogaine (p < 0.1558) (p < 0.3763), respectively. Furthermore, ibogaine itself did not significantly alter NAcc DA release over the 2-h period studied (p < 0.9113) although individual time points were significantly affected bidirectionally. Concurrently ibogaine significantly increased 5-HT release (p < 0.0155). Behaviorally, ibogaine appears to be a weak psychostimulant. The data show a critical modulatory role for 5-HT in ibogaine-cocaine interactions. Also elucidated as critical is the efficacy of ibogaine when the response to (SC) cocaine is decreased due to the habituation of the animals to their environment RP - NOT IN FILE SP - 711 EP - 728 VL - 49 ER - TY - JOUR AU - Cappendijk,S.L. AU - Fekkes,D. AU - Dzoljic,M.R. TI - The inhibitory effect of norharman on morphine withdrawal syndrome in rats: comparison with ibogaine KW - ibogaine KW - Morphine KW - Rats KW - Animal KW - Arousal KW - drug effect KW - Physiology KW - Brain KW - Physiopathology KW - Comparative Study KW - Harmine KW - Analogs & Derivatives KW - Pharmacology KW - Male KW - Toxicity KW - Naloxone KW - Rats,Wistar KW - Receptors,Opioid KW - Substance Withdrawal Syndrome KW - Prevention & Control KW - Support,Non-U.S.Gov't KW - Grooming KW - Withdrawal JO - Behav Brain Res PY - 1994 AB - Norharman (20 mg/kg, i.p.) and ibogaine (40 mg/kg, i.p.) significantly attenuated naloxone (4 mg/kg, i.p.)-precipitated withdrawal syndrome in morphine-dependent rats. Several withdrawal signs, such as teeth-chattering, chewing, penile licking and diarrhoea, were decreased by both norharman and ibogaine. In addition, norharman reduced also the withdrawal grooming and rearing. It is concluded that both norharman and ibogaine are inhibitors of withdrawal syndrome in morphine- dependent rats RP - NOT IN FILE SP - 117 EP - 119 VL - 65 ER - TY - JOUR AU - Glick,S.D. AU - Kuehne,M.E. AU - Raucci,J. AU - Wilson,T.E. AU - Larson,D. AU - Keller,R.W. AU - Carlson,J.N. TI - Effects of Iboga Alkaloids on Morphine and Cocaine Self Administration in Rats Relationship to Tremorigenic Effects and to Effects on Dopamine Release in Nucleus Accumbens and Striatum KW - Glick KW - ibogaine KW - Harmaline KW - Tabernanthine KW - Coronaridine KW - Ibogamine KW - Desethylcoronaridine KW - Morphine KW - Cocaine KW - Drug Self-Administration KW - PARASAGITTAL ZONES KW - D-AMPHETAMINE KW - Brain KW - LESIONS KW - alkaloid KW - Addiction KW - Self Administration KW - Rats KW - Tremor KW - Dopamine KW - Nucleus Accumbens KW - Striatum KW - Microdialysis KW - Dopamine Release KW - Iboga Alkaloid KW - RELEASE KW - DRUGS KW - Neurotoxicity KW - INVOLVEMENT KW - SYSTEM KW - METABOLITES KW - Self-Administration KW - EXTRACELLULAR DOPAMINE JO - Brain Res PY - 1994 AB - Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addiction to opioid and stimulant drugs and has been reported to decrease morphine and cocaine self- administration in rats. The present study sought to determine if other iboga alkaloids, as well as the chemically related harmala alkaloid harmaline, would also reduce the intravenous self- administration of morphine and cocaine in rats. Because both ibogaine and harmaline induce tremors, an effect that may be causally related to neurotoxicity in the cerebellar vermis, the temorigenic activities of the other iboga alkaloids were assessed. Lastly, in view of the involvement of the dopaminergic mesolimbic system in the actions of drugs of abuse, the effects of some of the iboga alkaloids on extracellular levels of dopamine and its metabolites in the nucleus accumbens and striatum were determined. All of the tested alkaloids (i.e., ibogaine, tabernanthine, R- and S-coronaridine, R- and S- ibogamine, desethylcoronaridine, and harmaline) dose-dependently (2.5-80 mg/kg) decreased morphine and cocaine intake in the hour after treatment; decreases in morphine and cocaine intake intake were also apparent the day after administration of some but not all of these alkaloids (i.e., ibogaine, tabernanthine, desethylcoronaridine, and the R-isomers of coronaridine and ibogamine). In some rats, there were persistent decreases in morphine or cocaine intake for several days after a single injection or after two or three weekly injections of one or another of these alkaloids; R-ibogamine produced such effects more consistently than any of the other alkaloids. At the doses used to assess effects on drug self-administration, ibogaine, tabernanthine, desethylcoronaridine and harmaline all induced tremors for at least 2-3 h; both enantioners of both coronaridine and ibogamine induced very weak no tremors. Using in vivo microdialysis, the effects of the R- and S-enantiomers of coronaridine and ibogamine on extracellular dopamine levels in the nucleus accumbaens and striatum were compared. The R- entantiomers decreased dopamine levels in both brain regions whereas the S-enantiomers produced no significant changes in dopamine levels in either region. The results of this study indicate that the 'anti-addictive' and tremorigenic effects of the iboga alkaloids can be dissociated and that long-term effects of these alkaloids on drug self-administration appear to be related to initial decreases in dopaminergic activity in specific brain areas RP - NOT IN FILE SP - 14 EP - 22 VL - 657 ER - TY - JOUR AU - Harsing,L.G.,Jr. AU - Sershen,H. AU - Lajtha,A. TI - Evidence that ibogaine releases dopamine from the cytoplasmic pool in isolated mouse striatum KW - ibogaine KW - Dopamine KW - Animal KW - Cytoplasm KW - drug effect KW - Metabolism KW - Dopamine Antagonists KW - Pharmacology KW - Dopamine Uptake Inhibitors KW - Electric Stimulation KW - Male KW - Mice KW - Mice,Inbred BALB C KW - Neostriatum KW - Cytology KW - Nerve Endings KW - Neurons KW - Nucleus Accumbens KW - Sodium Channels KW - 3,4-Dihydroxyphenylacetic Acid KW - Tritium KW - Cocaine KW - Ligands KW - MOUSE KW - Striatum KW - DRUGS KW - RELEASE KW - Perfusion KW - RECEPTORS KW - METABOLITES KW - INHIBITION JO - J Neural Transm Gen Sect PY - 1994 AB - We measured the effect of ibogaine on the tritium efflux from isolated mouse striatum preloaded with [3H]dopamine ([3H]DA). Ibogaine increased the basal tritium outflow in a concentration- dependent manner, but it was without effect on electrical stimulation-induced tritium overflow. Separation of the released radioactivity after ibogaine administration showed that this drug increased the release of [3H]DA and [3H]-dihydroxyphenylacetic acid ([3H]DOPAC), but the efflux of O-methylated-deaminated metabolites was not changed. The dopamine (DA)-releasing effect of ibogaine was reduced by the DA uptake inhibitors cocaine and nomifensine. The tritium efflux evoked by ibogaine was not altered by omission of Ca2+ from the perfusion buffer or by inhibition of the voltage-sensitive Na+ channels with tetrodotoxin. Ibogaine maintained its effect on release from superfused striatum prepared from reserpine-pretreated mice. The ibogaine-induced tritium release measured from mouse striatum that was preloaded with [3H]DA was not affected by the D-2 DA receptor ligands (-)-quinpirole and (+/-)-sulpiride, indicating that the ibogaine-induced release is not subject to presynaptic autoreceptor regulation. Ibogaine failed to affect [3H]DA uptake and retention in mouse striatum. These data indicate that at the nerve terminal level ibogaine releases DA, and the primary source for the release is probably the cytoplasmic pool. The DA- releasing effect of ibogaine may have importance in mediation of its hallucinogenic action, as seen in a frequent practice in African cults RP - NOT IN FILE SP - 215 EP - 225 VL - 96 ER - TY - JOUR AU - Popik,P. AU - Layer,R.T. AU - Skolnick,P. TI - The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex KW - ibogaine KW - Animal KW - Binding,Competitive KW - drug effect KW - Dizocilpine Maleate KW - Antagonists & Inhibitors KW - Pharmacokinetics KW - Pharmacology KW - In Vitro KW - Ion Channels KW - Metabolism KW - Ligands KW - Phencyclidine KW - Analogs & Derivatives KW - Rats KW - Receptors,Glutamate KW - Receptors,N-Methyl-D-Aspartate KW - Morphine KW - DRUGS KW - RECEPTORS KW - MK-801 KW - SENSITIZATION KW - NMDA Receptor KW - RECEPTOR COMPLEX KW - COMPLEX KW - TOLERANCE KW - BEHAVIOR KW - BLOCKADE JO - Psychopharmacology PY - 1994 AB - Ibogaine is a putative anti-addictive drug with potential efficacy for the treatment of opiate, stimulant, and alcohol abuse. We now report ibogaine is a competitive inhibitor (Ki, 1.01 +/- 0.1 microM) of [3H]MK-801 binding to N-methyl-D- aspartate (NMDA) receptor coupled cation channels. Since MK-801 can attenuate the development of tolerance to morphine and alcohol as well as sensitization to stimulants in preclinical studies, the reported ability of ibogaine to modify drug-seeking behavior in man may be attributable to a blockade of NMDA receptor coupled cation channels RP - NOT IN FILE SP - 672 EP - 674 VL - 114 ER - TY - JOUR AU - Sershen,H. AU - Hashim,A. AU - Lajtha,A. TI - Ibogaine reduces preference for cocaine consumption in C57BL/6By mice KW - ibogaine KW - Cocaine KW - Mice KW - Animal KW - Brain KW - drug effect KW - Metabolism KW - Pharmacokinetics KW - Drinking KW - Therapeutic Use KW - Male KW - Mice,Inbred C57BL KW - Motor Activity KW - Stereotyped Behavior KW - Substance Dependence KW - Prevention & Control KW - Psychology KW - LOCOMOTOR-ACTIVITY KW - PREFERENCE KW - Locomotor Activity JO - Pharmacol Biochem Behav PY - 1994 AB - After a period of forced exposure to 300 mg/l cocaine HCl in drinking water for a period of one week, followed by forced exposure to 200 mg/l cocaine for an additional week, male C57BL/6By mice developed a preference for cocaine when given a choice of drinking either water or a solution containing cocaine (200 mg/l). The mean daily intake of cocaine during the choice period was 26 +/- 1 mg/kg or, when expressed as the ratio of cocaine over total fluid intake, represented a cocaine preference of 71 +/- 2%. Administration of ibogaine HCl (40 mg/kg, two injections 6 h apart) two weeks after the beginning of the choice period reduced the cocaine preference for at least five days; the mean daily intake of cocaine was reduced by 38% (to 16 +/- 1 mg/kg per day; p < 0.05) and cocaine preference was reduced to 41 +/- 2% (cocaine fluid consumption/total fluid intake). An acute challenge injection of cocaine (25 mg/kg SC) produced a significant increase in cocaine-induced locomotor activity and stereotypy in mice previously exposed to cocaine in their drinking water (cocaine choice group). Five days after ibogaine administration, locomotor and stereotypy activity were significantly lower after a challenge injection of cocaine (25 mg/kg SC). Brain levels of cocaine 35 min after the challenge injection of cocaine were approximately 25% higher in ibogaine- treated mice (7.2 +/- 0.5 and 9.3 +/- 0.8 micrograms/g wet wt for water vs. mice treated with water plus ibogaine and 9.3 +/- 0.2 and 11.8 +/- 0.7 micrograms/g wet wt for cocaine drinking vs. cocaine drinking plus ibogaine treatment).(ABSTRACT TRUNCATED AT 250 WORDS) RP - NOT IN FILE SP - 13 EP - 19 VL - 47 ER - TY - JOUR AU - Sershen,H. AU - Hashim,A. AU - Lajtha,A. TI - Effect of ibogaine on serotonergic and dopaminergic interactions in striatum from mice and rats KW - ibogaine KW - Mice KW - Rats KW - Animal KW - Biological Transport KW - drug effect KW - Comparative Study KW - Corpus Striatum KW - Metabolism KW - Dopamine KW - Electric Stimulation KW - Pharmacology KW - In Vitro KW - Male KW - Mice,Inbred C57BL KW - Quinoxalines KW - Rats,Sprague-Dawley KW - Reference Values KW - Serotonin KW - Serotonin Agonists KW - Serotonin Antagonists KW - Sulpiride KW - Tritium KW - Tropanes KW - Agonists KW - RELEASE KW - Dopamine Release KW - MOUSE KW - RAT KW - Striatum KW - PRETREATMENT JO - Neurochem Res PY - 1994 AB - The effect of ibogaine (Endabuse, NIH 10567) on serotonin uptake and release, and on serotonergic modulation of dopamine release, was measured in striatal tissue from rats and mice. Two hours after treatment in vivo with ibogaine (40 mg/kg i.p.) the uptake of labeled [3H]serotonin and [3H]dopamine uptake in striatal tissue was similar in the ibogaine-treated animal to that in the control. The 5HT1B agonist CGS-12066A (10(-5) M) had no effect on stimulation-evoked tritium release from mouse or rat striatal tissue preloaded with [3H]serotonin; however, it elevated tritium efflux from striatal tissue preloaded with [3H]dopamine. This increase was not seen in mice treated with ibogaine 2 or 18 hours previously, or in rats treated 2 hours before. Dopamine autoreceptor responses were not affected by ibogaine pretreatment in either mouse or rat striatal tissue; sulpiride increased stimulation-evoked release of tritium from tissue preloaded with [3H]dopamine. The long-lasting effect of ibogaine on serotonergic functioning, in particular, its blocking of the 5HT1B agonist- mediated increase in dopamine efflux, may have significance in the mediation of its anti-addictive properties RP - NOT IN FILE SP - 1463 EP - 1466 VL - 19 ER - TY - JOUR AU - Sheppard,S.G. TI - A preliminary investigation of ibogaine: case reports and recommendations for further study KW - ibogaine KW - Adult KW - Alcoholism KW - Psychology KW - Rehabilitation KW - Case Report KW - Dose-Response Relationship,Drug KW - Female KW - Heroin Dependence KW - Human KW - Adverse Effects KW - Therapeutic Use KW - Male KW - Methadone KW - Substance Abuse Detection KW - Substance Withdrawal Syndrome KW - Drug Therapy KW - alkaloid KW - DRUGS KW - Withdrawal KW - Drug Abuse KW - Heroin KW - Substance Abuse JO - J Subst Abuse Treat PY - 1994 AB - A naturally occurring substance, ibogaine, was taken by seven individuals who were addicted to opiates. Ibogaine, an alkaloid with psychotropic effects at doses of 200-300 mg and above, was taken in single doses of 700-1800 mg by the subjects in the study. At the end of the 24-38-hr psychoactive period induced by the drug at these doses, none of the subjects displayed significant opiate withdrawal symptoms. At the lowest dose of 700 mg, one subject recontinued his drug abuse after 2 days; of the remaining six individuals who took 1,000 mg or above, two relapsed after a number of weeks, one reverted to intermittent heroin use, and three appear to have remained drug-free 14 weeks or more after undergoing this experimental treatment. Ibogaine may be of value in the present and could serve as a model for the development of improved agents for the treatment of substance abuse in the future RP - NOT IN FILE SP - 379 EP - 385 VL - 11 ER - TY - JOUR AU - Aceto,M.D. AU - Bowman,E.R. AU - Harris,L.S. AU - May,E.L. TI - Dependence studies of new compounds in the rhesus monkey, rat and mouse (1992). [Review] KW - ibogaine KW - Animal KW - drug screening KW - In Vitro KW - macaca mulatta KW - Male KW - narcotics KW - Pharmacology KW - Receptors,Opioid KW - drug effect KW - Substance Dependence KW - Psychology KW - RAT KW - MOUSE JO - NIDA Res Monogr PY - 1993 RP - NOT IN FILE SP - 459 EP - 516 VL - 132 ER - TY - JOUR AU - Cappendijk,S.L. AU - Dzoljic,M.R. TI - Inhibitory effects of ibogaine on cocaine self-administration in rats KW - ibogaine KW - Cocaine KW - Self Administration KW - Rats KW - Analysis of Variance KW - Animal KW - Brain KW - drug effect KW - Metabolism KW - Administration & Dosage KW - Disease Models,Animal KW - Drug Administration Schedule KW - Therapeutic Use KW - Male KW - Motor Activity KW - Rats,Wistar KW - Substance Dependence KW - Drug Therapy KW - Physiopathology KW - Support,Non-U.S.Gov't KW - Cocaine Self-Administration KW - Self-Administration KW - Half-Life KW - INVOLVEMENT KW - METABOLITES JO - Eur J Pharmacol PY - 1993 AB - In order to determine the potential anti-addictive properties of ibogaine, we used the cocaine self-administration model in rats. The results indicate that a single injection of ibogaine (40 mg/kg i.p.) produced a significant decrease of cocaine intake, which remained unaltered for more than 48 h. Since the half-life time of ibogaine is short, this might suggest the involvement of one or several active metabolites of ibogaine in cocaine intake. Repetitive administration of ibogaine on three consecutive days also induced a pronounced decrease of cocaine intake. However, a more prominent inhibitory effect on cocaine intake was observed in animals treated repeatedly with ibogaine (40 mg/kg i.p.), once each week for 3 consecutive weeks. These results indicate that ibogaine or its metabolite(s) is a long-lasting interruptor of cocaine dependence, which supports similar observations from uncontrolled clinical studies RP - NOT IN FILE SP - 261 EP - 265 VL - 241 ER - TY - JOUR AU - Glick,S.D. AU - Rossman,K. AU - Wang,S. AU - Dong,N. AU - Keller,R.W.,Jr. TI - Local effects of ibogaine on extracellular levels of dopamine and its metabolites in nucleus accumbens and striatum: interactions with D-amphetamine KW - ibogaine KW - Dopamine KW - Nucleus Accumbens KW - Animal KW - Corpus Striatum KW - drug effect KW - Metabolism KW - Dextroamphetamine KW - Administration & Dosage KW - Drug Synergism KW - Extracellular Space KW - Female KW - Microdialysis KW - Perfusion KW - Rats KW - Rats,Sprague-Dawley KW - Support,U.S.Gov't,P.H.S. KW - Brain KW - Striatum KW - EXTRACELLULAR DOPAMINE KW - Dopac KW - D-AMPHETAMINE KW - Amphetamine KW - MECHANISMS KW - METABOLITES KW - PRETREATMENT JO - Brain Res PY - 1993 AB - Systemic administration of ibogaine (40 mg/kg, i.p.) has been reported to induce both acute (1-3 h) and persistent (19-20 h) changes in extracellular levels of dopamine and its metabolites in the nucleus accumbens and striatum. In the present study, local administration of ibogaine to the striatum and nucleus accumbens produced effects that mimicked both the acute and persistent effects of systemic administration: perfusion with high concentrations (200 and 400 microM) of ibogaine mimicked the acute effects (decreased extracellular dopamine levels and increased extracellular metabolite levels) whereas perfusion with a low concentration (10 microM) of ibogaine mimicked the persistent effects (decreased extracellular levels of DOPAC). These results indicate that ibogaine acts directly in brain regions containing dopaminergic nerve terminals and that long- lasting effects of systemically administered ibogaine might be mediated by persisting low levels of ibogaine. Locally administered ibogaine (10 microM) was also found to enhance the effects of systemically administered D-amphetamine (1.25 mg/kg, i.p.) on extracellular dopamine levels, and conversely, systemically administered ibogaine (40 mg/kg, i.p.; 19 h pretreatment) enhanced the effects of locally administered D- amphetamine (1-10 microM). These results indicate that, in addition to a metabolic mechanism implicated previously, a pharmacodynamic mechanism contributes to the interaction between ibogaine and D-amphetamine. The relevance of such mechanisms to claims regarding ibogaine's anti-addictive properties is unclear RP - NOT IN FILE SP - 201 EP - 208 VL - 628 ER - TY - JOUR AU - O'Hearn,E. AU - Molliver,M.E. TI - Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline KW - ibogaine KW - Harmaline KW - Animal KW - Calcium-Binding Protein,Vitamin D-Dependent KW - Analysis KW - Metabolism KW - Cerebellum KW - drug effect KW - Pathology KW - Physiology KW - Toxicity KW - Male KW - Microtubule-Associated Proteins KW - Nerve Degeneration KW - Neurons KW - Neurotoxins KW - Purkinje Cells KW - Rats KW - Rats,Sprague-Dawley KW - Support,U.S.Gov't,P.H.S. KW - Indoles KW - alkaloid KW - Tremor KW - Cocaine KW - Human KW - Methods KW - Addiction KW - Astrocytes KW - DRUGS KW - RELEASE KW - Amino Acids KW - PARASAGITTAL ZONES KW - indole alkaloid KW - POTENT KW - Microglia JO - Neuroscience PY - 1993 AB - The indole alkaloids ibogaine and harmaline are beta-carboline derivatives that cause both hallucinations and tremor. Reports that ibogaine may have potent anti-addictive properties have led to initiatives that it be tested for the treatment of opiate and cocaine addiction. In this study, ibogaine-treated rats were analysed for evidence of neurotoxic effects because human clinical trials of ibogaine have been proposed. We recently found that ibogaine induces a marked glial reaction in the cerebellum with activated astrocytes and microglia aligned in parasagittal stripes within the vermis. Based on those findings, the present study was conducted to investigate whether ibogaine may cause neuronal injury or degeneration. The results demonstrate that, after treatment with ibogaine or harmaline, a subset of Purkinje cells in the vermis degenerates. We observed a loss of the neuronal proteins microtubule-associated protein 2 and calbindin co-extensive with loss of Nissl-stained Purkinje cell bodies. Argyrophilic staining of Purkinje cell bodies, dendrites and axons was obtained with the Gallyas reduced silver method for degenerating neurons. Degenerating neurons were confined to narrow parasagittal stripes within the vermis. We conclude that both ibogaine and harmaline have selective neurotoxic effects which lead to degeneration of Purkinje cells in the cerebellar vermis. The longitudinal stripes of neuronal damage may be related to the parasagittal organization of the olivocerebellar climbing fiber projection. Since these drugs produce sustained activation of inferior olivary neurons, we hypothesize that release of an excitatory amino acid from climbing fiber synaptic terminals may lead to excitotoxic degeneration of Purkinje cells RP - NOT IN FILE SP - 303 EP - 310 VL - 55 ER - TY - JOUR AU - O'Hearn,E. AU - Long,D.B. AU - Molliver,M.E. TI - Ibogaine induces glial activation in parasagittal zones of the cerebellum KW - ibogaine KW - Cerebellum KW - Animal KW - Astrocytes KW - drug effect KW - Behavior,Animal KW - Cerebellar Cortex KW - Cytology KW - Genes,MHC Class II KW - Glial Fibrillary Acidic Protein KW - Immunology KW - Metabolism KW - Pharmacology KW - Immunohistochemistry KW - Male KW - Neuroglia KW - Rats KW - Rats,Sprague-Dawley KW - Support,U.S.Gov't,P.H.S. KW - Tremor KW - Chemically Induced KW - Indoles KW - alkaloid KW - DRUGS KW - Addiction KW - MECHANISMS KW - PARASAGITTAL ZONES KW - indole alkaloid KW - SITES KW - Neurotoxicity KW - Microglia KW - CORTEX JO - Neuroreport PY - 1993 AB - Ibogaine, an indole alkaloid, has been proposed for treatment of drug addiction, yet its mechanism, site of action, and possible neurotoxicity have not been determined. Since neuronal injury is known to activate neurologlial cells, we investigated potential neurotoxic effects of this drug in rats by examining expression of specific glial markers. After treatment with ibogaine (100 mg kg-1 i.p.; 1-3 doses), we observed increased cytochemical markers in both microglia (OX-6, OX-42, W3/25) and astrocytes (GFAP), associated with striking morphologic changes in these cells. Activated glial cells were restricted to longitudinally oriented, parasagittal stripes within the vermis of cerebellar cortex. The ibogaine-induced activation of cerebellar glial cells is highly suggestive of neuronal degeneration, most likely of Purkinje cells RP - NOT IN FILE SP - 299 EP - 302 VL - 4 ER - TY - JOUR AU - Schechter,M.D. AU - Gordon,T.L. TI - Comparison of the behavioral effects of ibogaine from three sources: mediation of discriminative activity KW - ibogaine KW - Animal KW - Behavior,Animal KW - drug effect KW - Comparative Study KW - Discrimination KW - Psychology KW - Dose-Response Relationship,Drug KW - Pharmacology KW - Male KW - Rats KW - Rats,Sprague-Dawley KW - Serotonin Agonists KW - alkaloid KW - Dopamine KW - Dopamine Antagonists KW - DRUGS KW - STIMULI KW - ANTAGONIST KW - Drug Abuse KW - dose response JO - Eur J Pharmacol PY - 1993 AB - Ibogaine is an alkaloid employed for its hallucinatory properties in West Central Africa which has been the subject of alleged efficacy as an aid in the interruption and treatment of chemical dependency. The major sources of the Schedule I agent are: Sigma Chemical Co., the National Institute on Drug Abuse and as NDA International Inc.'s Endabuse. The intent of the present study was to, for the first time, train rats to discriminate the interoceptive stimuli produced by (10 mg/kg, intraperitoneally administered) ibogaine. Once trained, these rats were used to investigate the dose-response effects to ibogaine from each of the three suppliers. In addition, stimulus generalization to the dopamine antagonist CGS 10476B, as well as to the serotonergically active compounds fenfluramine, TFMPP (1-(m- trifluoromethylphenyl)piperazine, DOI (1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane), MDMA (3,4- methylenedioxymethamphetamine), quipazine and LSD, was tested. The results indicate that ibogaine is readily discriminable from its vehicle and that ibogaine from each of the three supplies produced statistically similar discrimination with ED50 values ranging from 2.5 to 3.4 mg/kg. In addition, various doses of the novel drugs tested produced, at best, intermediate ibogaine- appropriate responding and, thus, no drug tested can be considered to generalize to ibogaine-like stimuli. Discussion concerns the multiple actions of ibogaine that have been cited in the scientific literature. The similarity in potency of ibogaine from three potential suppliers should allow for pre-clinical work using any of these research samples to be comparable RP - NOT IN FILE SP - 79 EP - 84 VL - 249 ER - TY - JOUR AU - Schechter,M.D. TI - Cocaine discrimination is attenuated by isradipine and CGS 10746B KW - ibogaine KW - Cocaine KW - Animal KW - Antipsychotic Agents KW - Pharmacology KW - Calcium Channel Blockers KW - ANTAGONIST KW - Conditioning,Operant KW - drug effect KW - Discrimination KW - Psychology KW - Dose-Response Relationship,Drug KW - Isradipine KW - Male KW - Rats KW - Rats,Sprague-Dawley KW - Serotonin Antagonists KW - Thiazepines KW - Tropanes KW - Calcium KW - Analysis KW - Dopamine KW - MECHANISMS KW - RECEPTORS KW - Dopamine Release KW - RELEASE KW - discriminative stimulus KW - HT3 KW - dose response KW - PRETREATMENT KW - 5-HT3 RECEPTOR ANTAGONISTS KW - RECEPTOR ANTAGONIST JO - Pharmacol Biochem Behav PY - 1993 AB - The discriminative stimulus properties of cocaine are thought to be mediated by dopaminergic mechanisms that may be modulated by calcium ion influx and/or interact with 5-hydroxytryptamine3 (5- HT3) receptors. To test these possibilities, rats were trained to discriminate between the stimulus properties of 10.0 mg/kg cocaine and its vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-related decrease in discriminative performance when tested with lower cocaine doses. An analysis of the dose-response curve indicated an ED50 value of 3.04 mg/kg. Pretreatment with the presynaptic dopamine release- inhibiting agent CGS 10746B (20-40 mg/kg) resulted in a dose- related decrease in cocaine discrimination with the highest dose significantly attenuating cocaine discrimination. Pretreatment with 10-30 mg/kg isradipine, a calcium channel blocker, also resulted in a dose-related decrease in cocaine discriminative performance. In contrast to these positive results, pretreatment with the 5-HT3 receptor antagonist MDL 72222 (3.5-7.0 mg/kg), or the same doses of ibogaine, did not significantly affect cocaine discrimination. The results suggest that cocaine controls differential responding in a discriminative stimulus task by mechanisms that involve presynaptic release of dopamine, which may be regulated by neuronal calcium influx through L-type calcium channels RP - NOT IN FILE SP - 661 EP - 664 VL - 44 ER - TY - JOUR AU - Woods,J.H. AU - France,C.P. AU - Medzihradsky,F. AU - Smith,C.B. AU - Winger,G.D. TI - Evaluation of new compounds for opioid activity, 1992. [Review] KW - ibogaine KW - Animal KW - Anxiety KW - Psychology KW - Behavior,Animal KW - drug effect KW - Cocaine KW - Pharmacology KW - Dopamine KW - Metabolism KW - Electrochemistry KW - Environment KW - Habituation KW - Male KW - Microelectrodes KW - Motor Activity KW - Nucleus Accumbens KW - Anatomy & Histology KW - Rats KW - Rats,Sprague-Dawley KW - Serotonin KW - Stereotyped Behavior KW - Indoles KW - indole alkaloid KW - alkaloid KW - BEHAVIOR KW - Locomotor Activity KW - Grooming KW - RELEASE KW - BEHAVIORAL-RESPONSE JO - NIDA Res Monogr PY - 1993 AB - Ibogaine, a serotonergic (5-HTergic) indole alkaloid, was studied for cocaine modulatory effects on four parameters of behavior by computerized infrared photocell beam detection. The behavioral parameters were: a) locomotor activity (ambulations), b) rearing, c) stereotypy (fine movements, primarily grooming), and d) agoraphobia [(thigmotaxis) a natural tendency to avoid the center of the behavioral chamber]. With each behavioral data point, dopamine (DA) release, and serotonin (5-HT) release were detected within seconds in nucleus accumbens (NAcc) of the same behaving male Sprague-Dawley rats, using in vivo electrochemistry (voltammetry). Ibogaine was administered (40 mg/kg IP) for 4 consecutive days. Importantly, the DAergic and the 5-HTergic responses to (SC) cocaine and two behavioral responses, ambulations and central ambulations, were reduced in intensity due to extended time spent in the novel behavioral chamber (habituated). Rearing and fine movement patterns were not habituated. The results show that ibogaine downmodulated the (SC) cocaine-induced increase in NAcc DA release (p < 0.0001) and potentiated the (SC) cocaine-induced decrease in NAcc 5-HT release (p < 0.0001). Concurrently, ibogaine downmodulated cocaine-induced ambulation (p < 0.0001) and central ambulation behavior (p < 0.0001). On the other hand, the behavioral parameters that did not exhibit habituation, i.e., rearing behavior and fine movement behavior, were not downmodulated by ibogaine (p < 0.1558) (p < 0.3763), respectively. Furthermore, ibogaine itself did not significantly alter NAcc DA release over the 2-h period studied (p < 0.9113) although individual time points were significantly affected bidirectionally. Concurrently ibogaine significantly increased 5-HT release (p < 0.0155). Behaviorally, ibogaine appears to be a weak psychostimulant. The data show a critical modulatory role for 5-HT in ibogaine-cocaine interactions. Also elucidated as critical is the efficacy of ibogaine when the response to (SC) cocaine is decreased due to the habituation of the animals to their environment RP - NOT IN FILE SP - 517 EP - 578 VL - 132 ER - TY - JOUR AU - Aceto,M.D. AU - Bowman,E.R. AU - Harris,L.S. AU - May,E.L. TI - Dependence studies of new compounds in the rhesus monkey and mouse (1991). [Review] KW - ibogaine KW - Animal KW - Behavior,Animal KW - drug effect KW - narcotics KW - Pharmacology KW - MOUSE KW - rhesus monkey JO - NIDA Res Monogr PY - 1992 RP - NOT IN FILE SP - 513 EP - 558 VL - 119 ER - TY - JOUR AU - Deecher,D.C. AU - Teitler,M. AU - Soderlund,D.M. AU - Bornmann,W.G. AU - Kuehne,M.E. AU - Glick,S.D. TI - Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies KW - ibogaine KW - Harmaline KW - Animal KW - Brain KW - Metabolism KW - Cattle KW - Pharmacology KW - Ion Channels KW - Kinetics KW - Membrane Proteins KW - drug effect KW - Neurons KW - Radioligand Assay KW - Methods KW - Rats KW - Receptors,Adrenergic,alpha KW - Receptors,Adrenergic,beta KW - Receptors,Cell Surface KW - Receptors,Dopamine KW - Receptors,Drug KW - Receptors,GABA-A KW - Receptors,Muscarinic KW - Receptors,Nicotinic KW - Receptors,Opioid KW - Receptors,Serotonin KW - Support,Non-U.S.Gov't KW - Support,U.S.Gov't,P.H.S. KW - Tritium KW - Harmine KW - Sodium Channels KW - RECEPTORS KW - Coronaridine KW - Tabernanthine KW - Ibogamine KW - Recovery KW - DRUGS KW - MECHANISMS KW - CONGENERS KW - Radioligand Binding KW - OPIATE RECEPTORS KW - SODIUM KW - METABOLITES JO - Brain Res PY - 1992 AB - Assays using radioligands were used to assess the actions of ibogaine and harmaline on various receptor types. Ibogaine congeners showed affinity for opiate receptors whereas harmaline and harmine did not. The Ki for coronaridine was 2.0 microM at mu- opiate receptors. The Kis for coronaridine and tabernanthine at the delta-opiate receptors were 8.1 and 3.1 microM, respectively. Ibogaine, ibogamine, coronaridine and tabernanthine had Ki values of 2.08, 2.6, 4.3 and 0.15 microM, respectively, for kappa-opiate receptors. Long-lasting, dose-dependent behavioral effects of ibogaine have been reported. The possibility that these effects were due to irreversible binding properties of ibogaine at kappa- receptors was considered; however, radioligand wash experiments showed a rapid recovery of radioligand binding after one wash. A voltage-dependent sodium channel radioligand demonstrated Ki values in the microM range for all drugs tested. Using radioligand binding assays and/or 36Cl- uptake studies, no interaction of ibogaine or harmaline with the GABA receptor- ionophore was found. The kappa-activity of ibogaine (or an active metabolite) may be responsible for its putative anti-addictive properties whereas the tremorigenic properties of ibogaine and harmaline may be due to their effects on sodium channels RP - NOT IN FILE SP - 242 EP - 247 VL - 571 ER - TY - JOUR AU - Frances,B. AU - Gout,R. AU - Cros,J. AU - Zajac,J.M. TI - Effects of ibogaine on naloxone-precipitated withdrawal in morphine-dependent mice KW - ibogaine KW - Mice KW - Animal KW - Drug Synergism KW - Pharmacology KW - Morphine KW - Morphine Dependence KW - Naloxone KW - Pain Measurement KW - Substance Withdrawal Syndrome KW - Support,Non-U.S.Gov't KW - DRUGS KW - Withdrawal KW - Opioid Withdrawal JO - Fundam Clin Pharmacol PY - 1992 AB - In naive mice, ibogaine at a tremorigenic dose (30 mg/kg, ip), did not produce antinociception but did potentiate the antinociceptive potency of morphine in the tail-flick test. In morphine-dependent mice, ibogaine did not eliminate withdrawal symptoms but significantly increased the number of repetitive vertical jumps induced by naloxone, whatever the duration of the chronic morphine treatment. By comparison, repetitive jumping induced by alpha-napthoxyacetic acid (alpha-NOAA), a non- convulsant drug which induced jumping without affecting other morphine-withdrawal signs, was not significantly modified by ibogaine. These results indicate that while acute antinociceptive effects of morphine are modulated by ibogaine, this drug, shown to alleviate opiate dependence in man, does not attenuate in mice opioid withdrawal manifestations RP - NOT IN FILE SP - 327 EP - 332 VL - 6 ER - TY - JOUR AU - Glick,S.D. AU - Gallagher,C.A. AU - Hough,L.B. AU - Rossman,K.L. AU - Maisonneuve,I.M. TI - Differential effects of ibogaine pretreatment on brain levels of morphine and (+)-amphetamine KW - ibogaine KW - Brain KW - Morphine KW - Animal KW - drug effect KW - Metabolism KW - Dextroamphetamine KW - Pharmacokinetics KW - Female KW - Half-Life KW - Pharmacology KW - Mass Fragmentography KW - Rats KW - Rats,Sprague-Dawley KW - Support,U.S.Gov't,P.H.S. KW - Amphetamine KW - PRETREATMENT JO - Brain Res PY - 1992 AB - Previous studies in rats have shown that ibogaine inhibits neurochemical and behavioral effects of morphine yet potentiates similar effects of (+)-amphetamine. To assess whether these different functional interactions have a metabolic basis, brain levels of morphine and (+)-amphetamine were measured by gas chromatography-mass spectrometry after ibogaine pretreatment (19 h before injection of morphine or (+)-amphetamine). Ibogaine pretreatment had no effect on brain morphine levels, either at 30 min or 2 h after morphine injection; however, ibogaine significantly increased brain amphetamine levels at 30 min and, to a greater extent, at 2 h after (+)-amphetamine injection. These and other data suggest that ibogaine irreversibly inhibits an amphetamine-metabolizing enzyme. The functional interactions between ibogaine and (+)-amphetamine, but not those between ibogaine and morphine, may result from a hepatic drug-drug interaction RP - NOT IN FILE SP - 173 EP - 176 VL - 588 ER - TY - JOUR AU - Glick,S.D. AU - Rossman,K. AU - Rao,N.C. AU - Maisonneuve,I.M. AU - Carlson,J.N. TI - Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor KW - ibogaine KW - Morphine KW - Rats KW - Tremor KW - Acute Disease KW - Animal KW - Pharmacology KW - Male KW - Adverse Effects KW - Rats,Inbred Strains KW - Substance Withdrawal Syndrome KW - Prevention & Control KW - Support,U.S.Gov't,P.H.S. KW - Chemically Induced KW - Human KW - Grooming KW - HUMANS KW - Withdrawal KW - Opioid Withdrawal JO - Neuropharmacology PY - 1992 AB - Because of the claim that ibogaine suppresses the symptoms of "narcotic withdrawal" in humans, the effect of ibogaine on naltrexone-precipitated withdrawal signs in morphine-dependent rats was assessed. Morphine was administered subcutaneously through implanted silicone reservoirs for 5 days. Ibogaine (20, 40 or 80 mg/kg, i.p.) or saline was administered 30 min prior to challenge with naltrexone (1 mg/kg, i.p.) and withdrawal signs were counted for the following 2 hr. Ibogaine (40 and 80 mg/kg) significantly reduced the occurrence of four signs (wet-dog shakes, grooming, teeth chattering and diarrhea) during naltrexone-precipitated withdrawal; three other signs (weight loss, burying and flinching) were unaffected. Ibogaine induces head and body tremors lasting for 2-3 hr and the tremors might have interfered with the expression of opioid withdrawal. To examine this issue, another experiment was conducted in which ibogaine (40 mg/kg) or saline was administered 4 hr prior to challenge with naltrexone. Although there was a complete absence of tremors, ibogaine still significantly reduced the occurrence of the same four signs of withdrawal RP - NOT IN FILE SP - 497 EP - 500 VL - 31 ER - TY - JOUR AU - Maisonneuve,I.M. AU - Rossman,K.L. AU - Keller,R.W.,Jr. AU - Glick,S.D. TI - Acute and prolonged effects of ibogaine on brain dopamine metabolism and morphine-induced locomotor activity in rats KW - ibogaine KW - Brain KW - Dopamine KW - Metabolism KW - Rats KW - Animal KW - drug effect KW - Female KW - Pharmacology KW - Morphine KW - Antagonists & Inhibitors KW - Motor Activity KW - Rats,Inbred Strains KW - Support,U.S.Gov't,P.H.S. KW - Time Factors KW - Homovanillic Acid KW - Nucleus Accumbens KW - Locomotion KW - Addiction KW - Dopac KW - HVA KW - Striatum KW - PREFRONTAL CORTEX KW - LOCOMOTOR-ACTIVITY KW - RELEASE KW - DEPRESSION KW - Locomotor Activity KW - SYSTEM KW - METABOLITES KW - CORTEX KW - PRETREATMENT JO - Brain Res PY - 1992 AB - Ibogaine, an indolalkylamine, proposed for use in treating opiate and stimulant addiction, has been shown to modulate the dopaminergic system acutely and one day later. In the present study we sought to systematically determine the effects of ibogaine on the levels of dopamine (DA) and the dopamine metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in tissue at several time points, between 1 h and 1 month post-injection. One hour after ibogaine- administration (40 mg/kg i.p.) a 50% decrease in DA along with a 37-100% increase in HVA were observed in all 3 brain regions studied: striatum, nucleus accumbens and prefrontal cortex. Nineteen hours after ibogaine-administration a decrease in DOPAC was seen in the nucleus accumbens and in the striatum. A week after administration of ibogaine striatal DOPAC levels were still reduced. A month after ibogaine injection there were no significant neurochemical changes in any region. We also investigated the effects of ibogaine pretreatment on morphine- induced locomotor activity, which is thought to depend on DA release. Using photocell activity cages we found that ibogaine pretreatment decreased the stimulatory motor effects induced by a wide range of morphine doses (0.5-20 mg/kg, i.p.) administered 19 h later; a similar effect was observed when morphine (5 mg/kg) was administered a week after ibogaine pretreatment. No significant changes in morphine-induced locomotion were seen a month after ibogaine pretreatment. The present findings indicate that ibogaine produces both acute and delayed effects on the tissue content of DA and its metabolites, and these changes coincide with a sustained depression of morphine-induced locomotor activity RP - NOT IN FILE SP - 69 EP - 73 VL - 575 ER - TY - JOUR AU - Maisonneuve,I.M. AU - Keller,R.W.,Jr. AU - Glick,S.D. TI - Interactions of ibogaine and D-amphetamine: in vivo microdialysis and motor behavior in rats KW - ibogaine KW - Microdialysis KW - Rats KW - Animal KW - Brain Chemistry KW - drug effect KW - Catecholamines KW - Metabolism KW - Dextroamphetamine KW - Pharmacology KW - Dialysis KW - Dopamine KW - Dose-Response Relationship,Drug KW - Drug Synergism KW - Female KW - Motor Activity KW - Rats,Inbred Strains KW - Support,U.S.Gov't,P.H.S. KW - Nucleus Accumbens KW - Amphetamine KW - Addiction KW - D-AMPHETAMINE KW - EXTRACELLULAR DOPAMINE KW - Striatum KW - MOTOR BEHAVIOR KW - BEHAVIOR KW - PRETREATMENT JO - Brain Res PY - 1992 AB - Ibogaine, an indolalkylamine, has been proposed for use in treating stimulant addiction. In the present study we sought to determine if ibogaine had any effects on the neurochemical and motor changes induced by D-amphetamine that would substantiate the anti-addictive claim. Ibogaine (40 mg/kg, i.p.) injected 19 h prior to a D-amphetamine challenge (1.25 mg/kg, i.p.) potentiated the expected rise in extracellular dopamine levels in the striatum and in the nucleus accumbens, as measured by microdialysis in freely moving rats. Using photocell activity cages, the same ibogaine pretreatment enhanced the stimulatory motor effects induced by a wide range of D-amphetamine doses (0.625, 1.25, 2.5 or 5 mg/kg, i.p.). These findings suggest that ibogaine might increase the reinforcing efficacy of D- amphetamine. However, since high doses of D-amphetamine can be aversive, the potentiation of D-amphetamine's effects by ibogaine might also lead to a decrease in the reinforcing efficacy of D- amphetamine RP - NOT IN FILE SP - 87 EP - 92 VL - 579 ER - TY - JOUR AU - Maisonneuve,I.M. AU - Glick,S.D. TI - Interactions between ibogaine and cocaine in rats: in vivo microdialysis and motor behavior KW - ibogaine KW - Cocaine KW - Rats KW - Microdialysis KW - Animal KW - Pharmacology KW - Dialysis KW - Dopamine KW - Metabolism KW - Drug Synergism KW - Female KW - Motor Activity KW - drug effect KW - Rats,Inbred Strains KW - Support,U.S.Gov't,P.H.S. KW - Nucleus Accumbens KW - EXTRACELLULAR DOPAMINE KW - Striatum KW - Addiction KW - MOTOR BEHAVIOR KW - BEHAVIOR KW - PRETREATMENT JO - Eur J Pharmacol PY - 1992 AB - To investigate a possible basis for the proposed anti-addictive property of ibogaine, the effects of an ibogaine (40 mg/kg i.p.) pretreatment on in vivo neurochemical and motor effects induced by cocaine (20 mg/kg i.p.) were studied. Ibogaine, administered 19 h earlier, potentiated the increase in extracellular dopamine levels in striatum and nucleus accumbens as well as the stimulated motor activity induced by cocaine. Although high doses of cocaine can become aversive by producing an anxiogenic reaction, it is unknown whether the potentiation of cocaine's effects by ibogaine would also cause aversion and lead to a decrease in cocaine addiction RP - NOT IN FILE SP - 263 EP - 266 VL - 212 ER - TY - JOUR AU - Palumbo,P.A. AU - Winter,J.C. TI - Stimulus effects of ibogaine in rats trained with yohimbine, DOM, or LSD KW - ibogaine KW - Rats KW - Animal KW - Conditioning,Operant KW - drug effect KW - Discrimination Learning KW - DOM KW - ANTAGONIST KW - Pharmacology KW - Generalization,Stimulus KW - Lysergic Acid Diethylamide KW - Male KW - Pizotyline KW - Rats,Inbred F344 KW - Receptors,Serotonin KW - Stimulation,Chemical KW - Support,U.S.Gov't,P.H.S. KW - Yohimbine KW - Agonists KW - Discrimination KW - DRUGS KW - RECEPTORS KW - INVOLVEMENT JO - Pharmacol Biochem Behav PY - 1992 AB - The stimulus effects of ibogaine were compared with those of yohimbine, an alpha 2-adrenoceptor antagonist, 2,5-dimethoxy-4- methylamphetamine (DOM), a 5-hydroxytryptamine2 (5-HT2) agonist, and lysergic acid diethylamide (LSD), a nonspecific 5-HT agonist. Rats were trained with either yohimbine (6 mg/kg), DOM (0.6 mg/kg), or LSD (0.1 mg/kg) vs. no treatment in a two-lever discrimination task. Tests of generalization were then conducted with ibogaine. In yohimbine-trained animals, 39.7% of responses following ibogaine (15 mg/kg) were on the drug-appropriate lever, but this response level was not significantly different from no treatment-appropriate responding. A response distribution that was significantly different from responding under both drug and no treatment training conditions was observed in DOM-trained rats after administration of 15 mg/kg ibogaine. Pizotyline (BC-105) blocked all DOM-appropriate responding produced by ibogaine. In LSD-trained animals, 20 mg/kg ibogaine mimicked LSD. Pizotyline blocked LSD-appropriate responding produced by ibogaine in five of six animals. The present data suggest the involvement of 5-HT2 receptor activity, and the possibility of a 5-HT1A contribution, in the stimulus properties of ibogaine RP - NOT IN FILE SP - 1221 EP - 1226 VL - 43 ER - TY - JOUR AU - Sershen,H. AU - Harsing,L.G.,Jr. AU - Hashim,A. AU - Lajtha,A. TI - Ibogaine reduces amphetamine-induced locomotor stimulation in C57BL/6By mice, but stimulates locomotor activity in rats KW - ibogaine KW - Mice KW - Rats KW - Amphetamine KW - Antagonists & Inhibitors KW - Pharmacology KW - Animal KW - Behavior,Animal KW - drug effect KW - Corpus Striatum KW - Metabolism KW - Dopamine KW - Drug Synergism KW - Female KW - Homovanillic Acid KW - Locomotion KW - Male KW - Mice,Inbred C57BL KW - Motor Activity KW - Rats,Inbred Strains KW - Stimulation,Chemical KW - Tritium KW - 3,4-Dihydroxyphenylacetic Acid KW - In Vitro KW - D-AMPHETAMINE KW - LOCOMOTOR-ACTIVITY KW - RELEASE KW - Locomotor Activity KW - METABOLITES KW - PRETREATMENT JO - Life Sci PY - 1992 AB - The effect of ibogaine hydrochloride on locomotor stimulation induced by d-amphetamine sulfate was tested in male C57BL/6By mice and in female Sprague-Dawley rats. In mice, locomotor stimulation induced by d-amphetamine at 1 or 5 mg/kg s.c. was reduced by prior administration of one or two injections of ibogaine (40 mg/kg), given 2 or 18 hours earlier. This reduction in locomotor activity persisted for two days. Locomotor stimulation induced by a higher dose (10 mg/kg) of d-amphetamine was not reduced by such prior administration of ibogaine. A lower dose of ibogaine (20 mg/kg) did not reduce the subsequent locomotor activity induced by d-amphetamine. Ibogaine decreased striatal dopamine levels, while d-amphetamine increased them. Ibogaine treatment (2 x 40 mg/kg, 18 hours apart) induced a decrease by 30% in the level of striatal dopamine and its metabolites measured in tissue extracts 3 hours after the second ibogaine injection. One hour after d-amphetamine (5 mg/kg) administration, the level of striatal dopamine increased by 26%. Although the level of striatal dopamine was initially lower in the ibogaine-pretreated mice, d-amphetamine (5 mg/kg) administration induced an increase in striatal dopamine and its metabolites. The effect of ibogaine seems to be species specific, since in rats pretreated with ibogaine 18 hours before d- amphetamine, locomotor stimulation induced by d-amphetamine was further increased. In addition, the in vitro electrical-evoked release of [3H]dopamine from striatal tissue was either unchanged or inhibited in the presence of d-amphetamine, and after ibogaine pretreatment in vivo, the release of tritium in the presence of d- amphetamine was inhibited or stimulated in mice and rats, respectively RP - NOT IN FILE SP - 1003 EP - 1011 VL - 51 ER - TY - JOUR AU - Sershen,H. AU - Hashim,A. AU - Harsing,L. AU - Lajtha,A. TI - Ibogaine antagonizes cocaine-induced locomotor stimulation in mice KW - ibogaine KW - Mice KW - Amphetamine KW - Pharmacology KW - Animal KW - Biogenic Amines KW - Metabolism KW - Brain KW - Cocaine KW - Administration & Dosage KW - Drug Administration Schedule KW - Male KW - Mice,Inbred C57BL KW - Motor Activity KW - drug effect KW - Dopamine KW - Binding Sites KW - In Vitro KW - LOCOMOTOR-ACTIVITY KW - DEPRESSION KW - Striatum KW - FRONTAL-CORTEX KW - Locomotor Activity KW - METABOLITES KW - CORTEX KW - SITES KW - SYSTEM JO - Life Sci PY - 1992 AB - Ibogaine (40 mg/kg i.p.), when given 2 hours before an acute injection of cocaine (25 mg/kg s.c.) to C57BL/6 mice, reduced the cocaine-induced locomotor stimulation. Such stimulation was also reduced in the ibogaine-treated mice when a second injection of cocaine was given 24 hr later. Thus, the reduction in locomotor activity was not just the short-term depression of locomotor activity seen after ibogaine administration. When mice were given a daily injection of cocaine for 3 days and ibogaine was given after the cocaine injection on day 3, and again on day 4, cocaine- induced locomotor activity was reduced three hours later on day 4. On days 5 and 9 of the cocaine administration, with no further ibogaine treatment ambulatory counts were still lower in the ibogaine-pretreated mice. Locomotor stimulation induced by amphetamine (10 mg/kg) was not affected by ibogaine. An acute injection of ibogaine resulted in a transient increase in turnover of dopamine, as indicated by the increase in the ratio of metabolites of the dopamine to dopamine, followed by a decrease in the metabolites in striatum and frontal cortex 24 hr later. In vivo treatment with ibogaine did not affect the binding of [3H]WIN 35,248 to the cocaine binding site in striatal tissue measured in vitro. In addition, ibogaine added in vitro had a weak affinity to the WIN 35,248 binding site (IC50 for cocaine = 120 nM and for ibogaine = 1,500 nM). The results suggest that ibogaine may have induced a selective change in the dopaminergic system that results in a decrease in responsiveness to cocaine that persisted for at least 1 week RP - NOT IN FILE SP - 1079 EP - 1086 VL - 50 ER - TY - JOUR AU - Woods,J.H. AU - Medzihradsky,F. AU - Smith,C.B. AU - Winger,G.D. AU - France,C.P. TI - Evaluation of new compounds for opioid activity (1991). [Review] KW - ibogaine KW - Animal KW - Behavior,Animal KW - drug effect KW - Female KW - macaca mulatta KW - Male KW - Mice KW - Rats KW - Substance Dependence KW - Psychology JO - NIDA Res Monogr PY - 1992 RP - NOT IN FILE SP - 559 EP - 603 VL - 119 ER - TY - JOUR AU - Aceto,M.D. AU - Bowman,E.R. AU - Harris,L.S. AU - May,E.L. TI - Dependence studies of new compounds in the rhesus monkey and mouse (1990). [Review] KW - ibogaine KW - rhesus monkey KW - MOUSE KW - review JO - NIDA Res Monogr PY - 1991 RP - NOT IN FILE SP - 640 EP - 681 VL - 105 ER - TY - JOUR AU - Glick,S.D. AU - Rossman,K. AU - Steindorf,S. AU - Maisonneuve,I.M. AU - Carlson,J.N. TI - Effects and aftereffects of ibogaine on morphine self- administration in rats KW - ibogaine KW - Morphine KW - Self Administration KW - Rats KW - Animal KW - Behavior,Animal KW - drug effect KW - Conditioning,Operant KW - Female KW - Pharmacology KW - Rats,Inbred Strains KW - Support,U.S.Gov't,P.H.S. KW - alkaloid KW - Tremor KW - DRUGS KW - Reinforcement KW - Self-Administration KW - MOTOR BEHAVIOR K