Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Aminopyridine / pharmacology
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Acetamides / pharmacology*
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Action Potentials / drug effects*
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Action Potentials / physiology
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Animals
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Anticonvulsants / pharmacology*
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Carbamazepine / pharmacology
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Dose-Response Relationship, Drug
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Epilepsy / drug therapy*
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Epilepsy / metabolism
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Epilepsy / physiopathology
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Excitatory Amino Acid Antagonists / pharmacology
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Hippocampus / drug effects*
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Hippocampus / metabolism
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Hippocampus / physiopathology
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Magnesium Deficiency / physiopathology
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Male
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Neurons / drug effects*
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Neurons / metabolism
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Phenethylamines / pharmacology*
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Pyridines / pharmacology
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Rats
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Rats, Wistar
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / metabolism
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Sodium Channel Blockers
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Sodium Channels / metabolism
Substances
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Acetamides
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Anticonvulsants
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Excitatory Amino Acid Antagonists
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Phenethylamines
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Pyridines
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Receptors, N-Methyl-D-Aspartate
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Sodium Channel Blockers
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Sodium Channels
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alpha-phenyl-2-pyridineethanamine dihydrochloride
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FPL 12495
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Carbamazepine
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4-Aminopyridine
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remacemide