Differential effects of remacemide and desglycinyl-remacemide on epileptiform burst firing in the rat hippocampal slice.
Remacemide is a potential anticonvulsant drug with an active metabolite, desglycinyl-remacemide (DGR). Both moieties have been reported to block neuronal Na(+) channels and the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. The effects of remacemide and DGR on zero Mg(2+)/4-aminopyridine-induced epileptiform discharges were investigated in the rat hippocampal slice preparation and compared with carbamazepine (CBZ), a prototypic Na(+) channel blocker, and AR-R15896AR, a putative NMDA channel blocker. Remacemide (0-100 microM) was without significant effect, while DGR, CBZ and AR-R15896AR all decreased burst frequency in a concentration (0-100 microM) dependent manner. These findings suggest that remacemide is not sufficiently potent at the Na(+) channel or NMDA receptor to attenuate epileptiform activity in this model and that the anticonvulsant effects of the drug may be mediated by DGR.
Santangeli
Sarah
S
Epilepsy Unit, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, Scotland, UK.
Sills
Graeme J
GJ
Stone
Trevor W
TW
Brodie
Martin J
MJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000081:Acetamides / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008275:Magnesium Deficiency / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism
D000081:Acetamides; D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D010627:Phenethylamines; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C096406:alpha-phenyl-2-pyridineethanamine dihydrochloride; C089135:FPL 12495; D002220:Carbamazepine; D015761:4-Aminopyridine; C067553:remacemide