Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies.
D C Deecher, M Teitler, D M Soderlund, W G Bornmann, M E Kuehne, S D Glick
Brain research February 7, 1992 DOI: 10.1016/0006-8993(92)90661-r via PubMed
Summary
AI-generated from the abstractIbogaine and related compounds bind to various opioid receptors, with ibogaine showing affinity for kappa-opiate receptors (Ki = 2.08 µM), while harmaline and harmine do not bind to opiate receptors. All tested drugs also affect sodium channels at micromolar concentrations, but neither ibogaine nor harmaline interacts with GABA receptors. The kappa-opioid activity may explain ibogaine's proposed anti-addictive effects, while sodium channel effects could account for the tremor-inducing properties of ibogaine and harmaline.
Study at a glance
| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Citations | 143 |
| Key finding | Ibogaine binds to kappa-opiate receptors (Ki = 2.08 µM) and sodium channels, but not GABA receptors, suggesting its anti-addictive and tremorigenic effects arise from distinct mechanisms. |
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.