Na(+) channel effects of remacemide and desglycinyl-remacemide in rat cortical synaptosomes.
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.
Santangeli
Sarah
S
Epilepsy Unit, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, Scotland, UK.
Sills
Graeme J
GJ
Thompson
George G
GG
Brodie
Martin J
MJ
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000077213:Lamotrigine; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D000081:Acetamides; D000927:Anticonvulsants; D010627:Phenethylamines; D015222:Sodium Channels; D014227:Triazines; C089135:FPL 12495; D002220:Carbamazepine; D013779:Tetrodotoxin; D010672:Phenytoin; D014701:Veratridine; D012964:Sodium; C067553:remacemide; D000077213:Lamotrigine