Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin

Deborah C. Mash, Julie K. Staley, Michael H. Baumann, Richard B. Rothman, W. Lee Hearn

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)PL45-PL50
JournalLife Sciences
Volume57
Issue number3
DOIs
StatePublished - Jun 9 1995

Keywords

  • 12-hydroxyibogamine
  • desmethyl ibogaine
  • microdialysis
  • serotonin transporters

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology

Fingerprint Dive into the research topics of 'Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin'. Together they form a unique fingerprint.

  • Cite this