Deecher D C, Teitler M, Soderlund D M, Bornmann W G, Kuehne M E, Glick S D
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
Brain Res. 1992 Feb 7;571(2):242-7. doi: 10.1016/0006-8993(92)90661-r.
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.
使用放射性配体的分析方法用于评估伊博格碱和哈尔满对各种受体类型的作用。伊博格碱同系物对阿片受体显示出亲和力，而哈尔满和哈尔明则没有。在μ-阿片受体上，柯诺里定的Ki值为2.0微摩尔。在δ-阿片受体上，柯诺里定和沃氏夹竹桃碱的Ki值分别为8.1和3.1微摩尔。对于κ-阿片受体，伊博格碱、伊博加明、柯诺里定和沃氏夹竹桃碱的Ki值分别为2.08、2.6、4.3和0.15微摩尔。据报道，伊博格碱具有持久的、剂量依赖性的行为效应。曾考虑过这些效应可能是由于伊博格碱在κ-受体上的不可逆结合特性所致；然而，放射性配体洗脱实验表明，一次洗脱后放射性配体结合迅速恢复。一种电压依赖性钠通道放射性配体显示，所有测试药物的Ki值都在微摩尔范围内。使用放射性配体结合分析和/或36Cl摄取研究，未发现伊博格碱或哈尔满与GABA受体-离子载体有相互作用。伊博格碱（或一种活性代谢物）的κ-活性可能是其假定的抗成瘾特性的原因，而伊博格碱和哈尔满的致震颤特性可能是由于它们对钠通道的作用。
