Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2 papers in the library · 111 citations · publishing 1995-1998
Ibogaine binds moderately to sigma-2 receptors (Ki = 201 nM) and weakly to sigma-1 receptors (Ki = 8554 nM), showing 43-fold selectivity for sigma-2. Related compounds tabernanthine and ibogamine also bind sigma-2 with similar affinity but have higher sigma-1 affinity, resulting in about 14-fold selectivity. A potential ibogaine metabolite, O-des-methyl-ibogaine, has much weaker sigma-2 affinity (Ki = 5226 nM) and no significant sigma-1 affinity. Coronaridine and harmaline lack significant affinity for either sigma subtype. These findings suggest sigma-2 receptors may contribute to ibogaine's effects.
Ibogaine, a hallucinogen with potential for treating addiction, produces its effects through interactions with multiple brain receptors. In rats trained to recognize ibogaine, ligands targeting sigma2 and opiate receptors partially reproduced ibogaine's effects, while sigma1-selective agents did not. Morphine and kappa-selective opioids failed to substitute for ibogaine, but mixed-action opiates like (-)-SKF 10,047 and nalorphine showed intermediate generalization. Naloxone partially blocked ibogaine's effects and fully blocked those of (-)-SKF 10,047 and nalorphine. Neither PCP nor MK-801 substituted for ibogaine, indicating NMDA receptors are not involved. The findings suggest that sigma2 and opiate receptors, but not NMDA receptors, contribute to ibogaine's discriminative stimulus.