Chapter 2 Mechanisms of action of ibogaine: Relevance to putative therapeutic effects and development of a safer iboga alkaloid congener

Abstract

Publisher Summary Ibogaine, an alkaloid extracted from Tabernanthe iboga (Apocynaceae), is being used in uncontrolled clinical trials as a long-acting treatment for opioid and stimulant abuse, alcoholism, and smoking. In this study, animal models have been used to study ibogaine's interactions with drugs of abuse, to investigate its mechanisms of action, and to help develop an ibogaine derivative that will have an improved safety profile. An outline illustrating the kinds of studies conducted is presented. The chapter describes the results of these studies with ibogaine and with 18-methoxycoronaridine (18-MC), a novel iboga alkaloid congener. The structures of ibogaine and 18-MC are presented. Ibogaine has an active metabolite, noribogaine, and both ibogaine and noribogaine appear to have multiple mechanisms of action in the nervous system. 18-MC also appears to have multiple targets. The acute intraperitoneal (i.p.) administration of either ibogaine or 18-MC, 15 minutes prior to testing, dose-dependently decreased the self-administration of morphine in rats. With respect to stimulant-induced locomotion, both ibogaine and 18-MC augmented the expression of locomotor behavior in response to cocaine and amphetamines. Plasma and tissue levels of both ibogaine and 18-MC have been determined using gas chromatography-mass spectrometry. Anecdotal reports in humans indicate that ibogaine can slow heart rate.