Na(+) channel effects of remacemide and desglycinyl-remacemide in rat cortical synaptosomes

Abstract

The effects of the novel anticonvulsant, remacemide hydrochloride and its active metabolite, desglycinyl-remacemide, on veratridine-induced Na(+) influx in rat cortical synaptosomes were investigated and compared to established Na(+) channel blocking antiepileptic drugs. Remacemide and desglycinyl-remacemide reduced veratridine-stimulated Na(+) influx to 30.7% (IC(50)=160.6 microM) and 13.2% (IC(50)=85.1 microM) of control, respectively. Carbamazepine, phenytoin and lamotrigine similarly reduced Na(+) influx to 20.1% (IC(50)=325.9 microM), 79.8% and 27.9% (IC(50)=23.0 microM) of control, respectively. Resting internal Na(+) concentrations were significantly increased by desglycinyl-remacemide (1 and 10 microM) and, conversely, decreased by desglycinyl-remacemide and carbamazepine (both 1000 microM). These studies support previous electrophysiological investigations, which suggest that remacemide and desglycinyl-remacemide exert their antiepileptic effects, at least in part, by an inhibitory action on voltage-gated Na(+) channels. Desglycinyl-remacemide may have an additional action on Na(+) homeostasis that merits further exploration.