PHARMACOLOGICAL SCREENING OF N3, N5 DIPHENYL 1, 4 DIHYDROPYRIDINE 3, 5 DICARBOHYDRAZIDE DERIVATIVES FOR IN VIVO ANTICONVULSANT AND SEDATIVE ACTIVITY

Abstract

Diethyl-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate (1A) and Diethyl-4-(4-hydroxyphenyl)-2, 6-dimethyl-1, 4dihydropyridine-3, 5dicarboxylate (1A’) were synthesized by the condensation of ethyl acetoacetate with formaldehyde and para hydroxy benzaldehyde for 1A and 1A’ respectively. From these intermediates, novel derivatives of 2, 6-dimethyl-N,N-diphenyl-1,4-dihydropyridine-3,5-dicarbohydrazide (2A-2D’) were prepared in the presence of methanol and respective phenyl hydrazine. In view of the biological activities possessed by 1,4-dihydropyridines, synthesized compounds were subjected to in vivo anticonvulsant and sedative activities. Anticonvulsant activity was evaluated using Maximal electroshock (MES) induced convulsion method and Pentylenetetrazole (PTZ) induced convulsion method. Sedative activity was assessed by two models namely, locomotor activity using actophotometer in mice and anxiolytic activity using the elevated plus maze in rats. Phenytoin and diazepam were taken as standards for anticonvulsant activity, Chlorpromazine and diazepam were used as standards for sedative activity. Dimethyl sulfoxide (DMSO) was used as control; activity of synthesized drugs was compared with that of standards. All the newly synthesized derivatives exhibited significant anticonvulsant activity and considerably low sedative activity.