Remacemide hydrochloride: a novel antiepileptic agent.
1. Remacemide hydrochloride has been shown to possess anticonvulsant activity in a wide range of animal models of epilepsy with ED50s in the 6-60 mg/kg range, depending on the species and route of administration. The compound also has been shown to be effective clinically as add-on therapy for partial seizures. 2. Degradation of remacemide yields the desglycinated metabolite that is approximately 2-fold more potent as an anticonvulsant agent than the parent drug. 3. Both compounds displace [3H]MK801 binding from the cerebral cortical membranes, and the metabolite is approximately 150-fold more potent in doing so than remacemide. This effect, together with the findings that the desglycinate reduces N-methyl-D-aspartate (NMDA)-induced depolarizations in a variety of preparations, suggests that the mechanism of action is through blockade of the channel site of the NMDA-receptor complex. 4. Remacemide and its metabolite, in common with other antiepileptic agents, block sustained repetitive-firing in cultured neurons. The metabolite also has been shown to decrease glutamate release from cortical slices. 5. Remacemide hydrochloride has neuroprotective properties when tested on models of cerebral ischemia. 6. The drug has low toxicity in contrast to other NMDA-channel-blocking compounds, such as MK801 and phencyclidine, probably because of its low affinity for the channel-binding site.
Davies
J A
JA
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
D000081:Acetamides / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000627:therapeutic use*; D001711:Biotransformation; D004827:Epilepsy / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy*
D000081:Acetamides; D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C067553:remacemide