Remacemide: current status and clinical applications.
Remacemide (RMC) is a non-competitive, low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist that does not cause the behavioural and neuropathological side effects seen with other NMDA receptor antagonists. RMC and its active metabolite, AR-R 12495 AR, which has moderate affinity for the NMDA receptor, also interact with voltage-dependent neuronal sodium channels. Both agents show efficacy in a variety of animal models of epilepsy, parkinsonism and cerebral ischaemia. There is no evidence for teratogenicity or genotoxicity. RMC delays the absorption of L-dopa and elevates the concentrations of drugs metabolised by the hepatic cytochrome P450 3A4 isoform. RMC and AR-R 12495 AR have moderate protein binding and linear pharmacokinetics. Controlled studies show evidence of efficacy in treating epilepsy and Parkinson's disease. Post-surgical outcomes in RMC-treated patients at risk for intra-operative cerebral ischaemia are also encouraging. Adverse effects are related to the gastrointestinal and central nervous systems. RMC is a promising drug with numerous potential applications for both acute or chronic conditions associated with glutamate-mediated neurotoxicity.
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Departments of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, K-478, Boston, MA 02215, USA. sschacht@caregroup.harvard.edu
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D000081:Acetamides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy; D007431:Intraoperative Complications; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D010627:Phenethylamines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D000081:Acetamides; D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010627:Phenethylamines; D016194:Receptors, N-Methyl-D-Aspartate; C089135:FPL 12495; C067553:remacemide