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

92 Citations (Scopus)

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
JournalLife Sciences
Volume57
Issue number3
DOIs
StatePublished - Jun 9 1995

Fingerprint

Ibogaine
Serotonin Plasma Membrane Transport Proteins
Metabolites
Serotonin
Opiate Alkaloids
Drug-Seeking Behavior
Pharmaceutical Preparations
Radioligand Assay
Dopamine Plasma Membrane Transport Proteins
Microdialysis
Nucleus Accumbens
noribogaine
Cocaine
Assays

Keywords

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

ASJC Scopus subject areas

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

Cite this

Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. / Mash, Deborah C; Staley, Julie K.; Baumann, Michael H.; Rothman, Richard B.; Lee Hearn, W.

In: Life Sciences, Vol. 57, No. 3, 09.06.1995.

Research output: Contribution to journalArticle

Mash, Deborah C ; Staley, Julie K. ; Baumann, Michael H. ; Rothman, Richard B. ; Lee Hearn, W. / Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. In: Life Sciences. 1995 ; Vol. 57, No. 3.
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