Benzodiazepine receptors are involved in tabernanthine-induced tremor: in vitro and in vivo evidence.
J H Trouvin, P Jacqmin, C Rouch, M Lesne, C Jacquot
European Journal of Pharmacology August 1, 1987 DOI: 10.1016/0014-2999(87)90287-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro binding assays and in vivo animal experiments Peer reviewed |
|---|---|
| Population | Rats (in vivo) and brain tissue preparations (in vitro) |
| Interventions | Tabernanthine Flunitrazepam Ro-15 1788 |
| Topics | Ibogaine |
| Keywords | Synaptosomes Animals Rats, inbred strains Tremor Alkaloids Bicuculline Flunitrazepam Receptors, gaba-a Behavior, animal Binding, competitive Female In vitro techniques |
| Key findings | Tabernanthine competitively inhibited specific flunitrazepam binding in vitro (IC50 150 microM), behaved as a benzodiazepine receptor inverse agonist in a discriminant binding assay, and produced tremor in vivo whose time course paralleled brain tabernanthine concentration (half-life 2 h). The tremor was reversibly inhibited by flunitrazepam or the benzodiazepine receptor antagonist Ro-15 1788, suggesting part of tabernanthine's action may involve benzodiazepine receptors. |
Abstract
Tabernanthine, an indol alkaloid, is structurally related to carbolines (harmane, harmaline) which, in vitro, displace specific flunitrazepam binding to brain benzodiazepine receptors. In vivo, both tabernanthine and carbolines cause a fine general tremor, suggesting that a possible interaction with benzodiazepine receptors could be involved in the activity of tabernanthine. This hypothesis was validated by the in vitro and in vivo antagonism of benzodiazepine by tabernanthine. In vitro, tabernanthine inhibited specific flunitrazepam binding in a competitive manner with an affinity (IC50 150 microM) in the same range as harmane. Tabernanthine appeared as a benzodiazepine receptor inverse agonist in a discriminant in vitro binding assay. In vivo, the time course of tremorigenic activity was related to the tabernanthine concentration in brain (half-life = 2 h). Moreover, tabernanthine-induced tremor was inhibited reversibly by flunitrazepam or by Ro-15 1788 (an antagonist of benzodiazepine-receptors). These results suggest that part of the action of tabernanthine may be mediated by an interaction at the benzodiazepine receptor level.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| 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. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cited by 13
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- 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. Brain Research September 19, 1994
- Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats. Pharmacology, Biochemistry, and Behavior November 1, 1995
- Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study. European Journal of Pharmacology June 18, 1991
- Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity. Psychopharmacology April 1, 1995
and 8 more in the library