Interaction of ibogaine with human a3b4 nicotinic receptors in different conformational states
The FASEB Journal April 1, 2012 Ilana Emert, Katarzyna M Targowska-Duda, Dominik Feuerbach et al.
Ibogaine inhibits calcium influx through human α3β4 nicotinic acetylcholine receptors with roughly nine times higher potency than phencyclidine (PCP). Radioligand binding shows ibogaine binds to a single site on the receptor with a dissociation constant of 0.46 μM, and it has slightly higher affinity for desensitized receptors than for resting ones. Docking studies indicate both compounds interact with a binding domain between the serine (position 6′) and valine/phenylalanine (position 13′) rings, primarily through van der Waals contacts, consistent with the measured enthalpic contribution. Entropic contributions suggest local conformational changes upon binding.