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 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.
Sweetnam
P M
PM
Novascreen, Oceanix Biosciences, Hanover, MD 21214, USA.
Lancaster
J
J
Snowman
A
A
Collins
J L
JL
Perschke
S
S
Bauer
C
C
Ferkany
J
J
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D005069:Evaluation Studies as Topic; D007050:Ibogaine / Q000494:pharmacology*; D007700:Kinetics; D011869:Radioligand Assay; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000517:prevention & control*
D002352:Carrier Proteins; D011955:Receptors, Drug; D011976:Receptors, Muscarinic; D017473:Receptors, Opioid, kappa; C061445:cocaine receptor; D007050:Ibogaine