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[Ca.sup.2+] influx, radioligand binding, and molecular docking approaches are utilized to compare the interaction of fluoxetine and paroxetine, two selective serotonin reuptake inhibitors (SSRIs), with the human (h) [alpha]4[beta]2, [alpha]3[beta]4, and [alpha]7 nicotinic acetylcholine receptors (AChRs) in different conformational states. The results suggested that SSRIs inhibit the most important neuronal AChRs with potencies and affinities that are clinically relevant by binding to a luminal site that are shared with tricyclic antidepressants.

The interaction of the agonist JN403 with the human (h) [alpha]7 nicotinic acetylcholine receptor (AChR) was compared to that for the competitive antagonist methyllycaconitine (MLA) to study the receptor selectivity of JN403 on the h[alpha]7, h[alpha]3[beta]4, and h[alpha]4[beta]2 AChRs. The results provide insight into the significance of the higher receptor specificity of JN403 for the treatment of [alpha]7-related disorders, including dementias, pain-related ailments, depression, anxiety, and wound healing.

Structural and functional methods were used to characterize the binding sites and the mechanisms of inhibition of bupropion on muscle-type nicotinic acetylcholine receptors (AChRs). The results suggested that interaction of bupropion with a luminal binding domain shared with PCP, located between the serine and valine rings is mediated primarily by entropy-driven process.