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.