Interaction of ibogaine with human alpha3beta4-nicotinic acetylcholine receptors in different conformational states.
The international journal of biochemistry & cell biology September 1, 2010 Hugo R Arias, Avraham Rosenberg, Katarzyna M Targowska-Duda et al. 29 citations
Ibogaine blocks human alpha3beta4-nicotinic acetylcholine receptors (AChRs) by binding to a site in the receptor's ion channel, with about nine times higher potency than phencyclidine (PCP). Ibogaine binds with relatively high affinity (Kd = 0.46 ± 0.06 μM) to a single site in the channel and dissociates more slowly from the desensitized receptor than from the resting one, which may prolong the desensitized state. PCP inhibits ibogaine binding, indicating overlapping binding sites between the serine and valine/phenylalanine rings. The interaction is mainly via van der Waals contacts, with local conformational changes suggested by entropic contributions. These findings suggest ibogaine's mechanism involves stabilizing the receptor in a shut-down state.