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.