Anticonvulsant effects of bis-1,4-dihydropyridines and the probable role of L-type calcium channels suggested by docking simulations

摘要: The influx/efflux of calcium (Ca2+) ions through channels in cellular membranes plays a pivotal role many physiological and physiopathological processes. Among these are those involved the physiopathology epileptic seizures. Hence, control permeability is considered strategy for development anticonvulsant drugs. According to previous reports, dihydropyridine derivatives have proven be Ca2+ channel blockers anticonvulsive properties, presumably by means their action on L-type (LCCs). aim present study was determine effects four bis-1,4-dihydropyridines (bis-DHPs) male CF1 mice (25–30 g bw) using two experimental models: maximal electroshock (MES, which induces convulsions with an alternating current 60 Hz) pentylenetetrazole administration (PTZ, 90 mg/kg administered i.p.). Additionally, binding mode explored docking 3-D model LCC. bis-DHPs herein tested showed protective effect relation number induced MES, recovery time after convulsion, duration tonic phase. However, only 01–03 reduced clonic phase, compounds also produced significant against PTZ administration. This may related interaction cluster aromatic residues (Tyr1152, Tyr1463, Phe1159) blocking flow, as suggested studies.