Klinische Pharmakologie / Psychopharmakologie




Abstracts aus der Fachpresse
(Auszug einer MedLine Recherche: 1992-1996)

Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity.

Bauer C Collins JL Ferkany J Lancaster J Perschke S Snowman A Sweetnam PM

Psychopharmacology (Berlin), 1995 April

Abstract: 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 microM. These included the mu, delta, kappa, opiate, 5HT2, 5HT3, and muscarinic1 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 [3H]MK-801 and [3H]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. -AA- Novascreen, Oceanix Biosciences, Hanover, MD 21214, USA.

Effects of ibogaine on naloxone-precipitated withdrawal in morphine-dependent mice.

Cros J Francés B Gout R Zajac JM

Fundam Clinical Pharmacology 1992

Abstract: 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. -AA- Laboratoire de Pharmacologie et de Toxicologie Fondamentales, CNRS, Toulouse, France.

The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex.

Layer RT, Popik P, Skolnick P

Psychopharmacology (Berlin), 1994 May, CU 95

Abstract: 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. -AA- Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892-0008.

A preliminary investigation of ibogaine: case reports and recommendations for further study.

Sheppard SG

J Substance Abuse Treat, 1994 Juli-August

Abstract: 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.

Neurochemical and behavioural interactions between ibogaine and nicotine in the rat.

Benwell ME, Holtom PE, Moran RJ, Balfour DJ

Br J Pharmacology, 1996 Februar

Abstract: 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. -AA- Department of Pharmacology and Clinical Pharmacology, University of Dundee Medical School, Ninewells Hospital.



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