Molecular Modeling and Potential Ca2+ Channel Blocker Activity of Diphenylmethoxypiperidine Derivatives

Abstract

Molecular interactions of 4-diphenylmethoxy-1-methylpiperidine derivatives with the calcium channel CaV1.1 (pdb:6JP5) are described. All the compounds tested, previously shown to inhibit adrenergic vascular contractions, display similar binding energetics and interactions with the trans-membrane domain of 6JP5 on the opposite side relative to the channel pore, where nifedipine, a known dihydropyridine Ca2+ channel blocker binds. Additionally, the compounds tested inhibit Ca2+-dependent contractions in isolated mouse mesenteric arteries. Thus, diphenylpyraline analogs may exert their anticontractile effects, at least partially, by blocking vascular Ca2+ channels.