IDENTIFICATION OF A PRIMARY METABOLITE OF IBOGAINE THAT TARGETS SEROTONIN TRANSPORTERS AND ELEVATES SEROTONIN

LIFE SCIENCES

卷:57

Letter

MASH, DC ; STALEY, JK ; BAUMANN, MH ; ROTHMAN, RB ; HEARN, WL

关键词: 12-HYDROXYIBOGAMINE;    SEROTONIN TRANSPORTERS;    MICRODIALYSIS;    DESMETHYL IBOGAINE;   

DOI  :  10.1016/0024-3205(95)00273-9

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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