Interaction of ibogaine with human a3b4 nicotinic receptors in different conformational states
Ilana Emert, Katarzyna M. Targowska‐duda, Dominik Feuerbach, Krysztof Jozwiak, Hugo R. Arias
The FASEB Journal April 1, 2012 Peer reviewed DOI: 10.1096/fasebj.26.1_supplement.762.1 via OpenAlex
Summary
Ibogaine inhibits Ca 2+ influx in human α3β4 nicotinic acetylcholine receptors with approximately 9-fold higher potency than phencyclidine (PCP). It binds to a single site with a high affinity of 0.46 μM and shows slightly higher affinity for desensitized receptors compared to resting ones. The binding interaction involves van der Waals contacts and is supported by docking studies, indicating local conformational changes.
Study at a glance
| Population | human α3β4 nicotinic acetylcholine receptors |
|---|---|
| Key finding | Ibogaine has ~9-fold higher potency than PCP in inhibiting epibatidine-induced Ca 2+ influx in human α3β4 nicotinic acetylcholine receptors. |
Abstract
The interaction of ibogaine and phencyclidine (PCP) with human (h) α3β4 nicotinic acetylcholine receptors (AChRs) in different conformational states was determined using radioligand binding assays, Ca 2+ influx detections, thermodynamic and kinetic measurements. The results show that ibogaine inhibits (±)‐epibatidine‐induced Ca 2+ influx in hα3β4 AChRs with ~9‐fold higher potency than PCP, [ 3 H]ibogaine binds to a single site in hα3β4 with relatively high affinity ( K d = 0.46 ± 0.006 μM), and ibogaine has slightly higher affinity for desensitized than resting hα3β4 AChRs, compared with PCP. These results correlate with the docking studies suggesting that ibogaine and PCP interact with a binding domain between the serine (position 6′) and valine/phenylalanine (position 13′) rings. This interaction is mediated mainly by van der Waals contacts, which is in agreement with the observed enthalpic contribution determined by non‐linear chromatography. Calculated entropic contribution also indicates local conformational changes. Research support came from the Science Foundation Arizona and Stardust Foundation.