Differential effects of remacemide and desglycinyl-remacemide on epileptiform burst firing in the rat hippocampal slice

Neurosci Lett. 2002 Mar 15;321(1-2):33-6. doi: 10.1016/s0304-3940(01)02511-3.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Acetamides / pharmacology*
  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Anticonvulsants / pharmacology*
  • Carbamazepine / pharmacology
  • Dose-Response Relationship, Drug
  • Epilepsy / drug therapy*
  • Epilepsy / metabolism
  • Epilepsy / physiopathology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Magnesium Deficiency / physiopathology
  • Male
  • Neurons / drug effects*
  • Neurons / metabolism
  • Phenethylamines / pharmacology*
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Sodium Channel Blockers
  • Sodium Channels / metabolism

Substances

  • Acetamides
  • Anticonvulsants
  • Excitatory Amino Acid Antagonists
  • Phenethylamines
  • Pyridines
  • Receptors, N-Methyl-D-Aspartate
  • Sodium Channel Blockers
  • Sodium Channels
  • alpha-phenyl-2-pyridineethanamine dihydrochloride
  • FPL 12495
  • Carbamazepine
  • 4-Aminopyridine
  • remacemide