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

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 μM. These included the mu, delta, kappa, opiate, 5HT₂, 5HT₃, and muscarinic_{1 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-α-benzoate binding (BTX-B), respectively. This broad spectrum of activity may in part be responsible for ibogaine's putative anti-addictive activity.