Ibogaine possesses a selective affinity for sigma 2 receptors.

Ibogaine, an alkaloid that may reduce cravings for addictive drugs, binds more strongly to sigma-2 receptors (Ki = 90.4 and 250 nM) than to sigma-1 receptors (Ki = 9310 nM). This suggests sigma-2 receptors could be its primary target in the central nervous system, and its low affinity for sigma-1 receptors makes it a promising starting point for developing drugs selective for sigma-2 receptors.

Study at a glance

Abstract

The alkaloid ibogaine is potentially useful to reduce craving for several drugs of abuse, but its mechanism of action is not known. In the current study, in vitro studies were conducted in order to determine the affinity of ibogaine for sigma receptors. Our results indicate that ibogaine has a relatively high affinity for sigma 2 receptors (Ki = 90.4 and 250 nM) and a significantly lower affinity for sigma 1 receptors (Ki = 9310 nM). These data suggest that ibogaine may have a higher affinity at sigma 2 receptors than any other known CNS receptor. Its low affinity for sigma 1 receptors also suggests that ibogaine may be a suitable lead compound for structure-activity relationship studies aimed at developing sigma 2-selective ligands.