Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity.

Ibogaine, an indole alkaloid being studied for treating cocaine and opioid addiction, interacts with a wide variety of neurotransmitter receptors and ion channels at concentrations of 1-100 microM. These include mu, delta, kappa opiate receptors, 5HT2, 5HT3, muscarinic1 and 2 receptors, and dopamine, norepinephrine, and serotonin uptake sites. It also affects NMDA-associated ion and sodium ion channels. This broad spectrum of activity may partly explain ibogaine's potential anti-addictive properties, though a clearly defined molecular mechanism has not been established.

Study at a glance

Abstract

The indole alkaloid ibogaine (NIH 10567, Endabuse) is currently being examined for its potential utility in the treatment of cocaine and opioid addiction. However, a clearly defined molecular mechanism of action for ibogaine's putative anti-addictive properties has not been delineated. Radioligand binding assays targeting over 50 distinct neurotransmitter receptors, ion channels, and select second messenger systems were employed to establish a broad in vitro pharmacological profile for ibogaine. These studies revealed that ibogaine interacted with a wide variety of receptors at concentrations of 1-100 microM. These included the mu, delta, kappa, opiate, 5HT2, 5HT3, and muscarinic1 and 2 receptors, and the dopamine, norepinephrine, and serotonin uptake sites. In addition, ibogaine interacted with N-methyl-D-aspartic acid (NMDA) associated ion and sodium ion channels as determined by the inhibition of [3H]MK-801 and [3H]bactrachotoxin A 20-alpha-benzoate binding (BTX-B), respectively. This broad spectrum of activity may in part be responsible for ibogaine's putative anti-addictive activity.