RECEPTOR-BINDING PROFILE SUGGESTS MULTIPLE MECHANISMS OF ACTION ARE RESPONSIBLE FOR IBOGAINES 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 mu M. These included the mu, delta, kappa, opiate, 5HT(2), 5HT(3), 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 [H-3]MK-801 and [H-3]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.