Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies.
Brain research – February 07, 1992
Source: PubMed
Summary
Ibogaine shows promise for anti-addictive properties, with its kappa-opiate receptor activity potentially driving these effects. In tests, ibogaine and its congeners displayed strong affinity for various opiate receptors, with Ki values of 2.08 µM for ibogaine at kappa receptors. Notably, coronaridine had a Ki of 2.0 µM at mu-opiate receptors and 4.3 µM at kappa receptors. Despite concerns about irreversible binding, experiments indicated rapid recovery of receptor binding, suggesting transient effects rather than permanent changes in receptor availability.
Abstract
Assays using radioligands were used to assess the actions of ibogaine and harmaline on various receptor types. Ibogaine congeners showed affinity for opiate receptors whereas harmaline and harmine did not. The Ki for coronaridine was 2.0 microM at mu-opiate receptors. The Kis for coronaridine and tabernanthine at the delta-opiate receptors were 8.1 and 3.1 microM, respectively. Ibogaine, ibogamine, coronaridine and tabernanthine had Ki values of 2.08, 2.6, 4.3 and 0.15 microM, respectively, for kappa-opiate receptors. Long-lasting, dose-dependent behavioral effects of ibogaine have been reported. The possibility that these effects were due to irreversible binding properties of ibogaine at kappa-receptors was considered; however, radioligand wash experiments showed a rapid recovery of radioligand binding after one wash. A voltage-dependent sodium channel radioligand demonstrated Ki values in the microM range for all drugs tested. Using radioligand binding assays and/or 36Cl- uptake studies, no interaction of ibogaine or harmaline with the GABA receptor-ionophore was found. The kappa-activity of ibogaine (or an active metabolite) may be responsible for its putative anti-addictive properties whereas the tremorigenic properties of ibogaine and harmaline may be due to their effects on sodium channels.