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 psychoactive alkaloid, is more potent than its analogs at blocking NMDA receptors, a brain target linked to addiction. In lab tests, ibogaine inhibited [3H]MK-801 binding to NMDA receptors most strongly (Ki ≈ 1.2 µM), while similar compounds like O-desmethylibogaine were less potent (Ki ≈ 5.5 µM) and O-t-butyl-O-desmethylibogaine much weaker (Ki ≈ 179 µM). In morphine-dependent mice, only ibogaine reduced withdrawal jumping triggered by naloxone, suggesting its anti-addictive effects stem from NMDA receptor antagonism.