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

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