Evaluation of anticonvulsant effect of two novels 4-[1-(4-fluorobenzyl) -5-imidazolyl] dihydropyridine derivatives in mice

Abstract

In this study the anticonvulsant effect of two dihydropyridine derivatives [diethyl -1,4- dihydro -2,6- dimethyl -4-(4- fluoro benzyl-2- methylthio -5- imidazolyl)-3,5- pyridine dicarboxilat (A) and diethyl -1,4- dihydro -2,6- diethyl -4-(4- fluoro benzyl-2- methylthio -5- imidazolyl)-3,5- pyridine dicarboxilat (B)] by pentylenetetrazole (PTZ) and electroshock in mice was evaluated. The latency and HLTE (hind limb tonic extensions), the duration of HLTE and the mortality protection in pentylenetetrazole test and the HLTE duration in electroshock test were assessed. Both compounds had significant differences with negative control in all doses used. There was no significant difference between nifedipine and B (96.7 and 169.2 mg/kg doses) in the starting point of HLTE and between nifedipine and A (62.2 and 108.9 mg/kg doses) in the duration of HLTE in the PTZ test. Also, there was no significant difference between nifedipine and B (96.7 and 169.2 mg/kg doses) and A (62.2 and 108.9 mg/kg doses) in electroshock test. All doses of A and B and nifedipine showed less effect than phenytoin and valproate. This study showed that both A and B have anticonvulsant activity in the PTZ-induced seizure model and the MES test. These compounds, thus, might be useful in the petit mal and grand mal epilepsy.