Dextrorphan and dextromethorphan, common antitussives, are antiepileptic and antagonize N-methyl-D-aspartate in brain slices.
The antitussive, dextromethorphan (DM), and its metabolite, dextrorphan (DX), were evaluated for antiepileptic properties in vitro. Interictal bursts and prolonged ictal epileptiform afterdischarges, induced by perfusion of guinea pig neocortical brain slices with Mg2+-free solution, were blocked by DX (1-250 microM) or DM (100 microM). Intracellular records showed that these agents blocked N-methyl-D-aspartate (NMDA)-induced depolarizations without altering intrinsic membrane properties. DX blocked NMDA but not quisqualate-evoked multi-unit excitatory responses. DM is a widely available, orally effective drug with low toxicity in antitussive doses, which has antiepileptic and NMDA-antagonist properties in vitro. Its toxicity and effectiveness as an anticonvulsant should be expeditiously examined in clinical trials.
D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000494:pharmacology*; D000996:Antitussive Agents / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D003915:Dextromethorphan / Q000378:metabolism / Q000494:pharmacology*; D003917:Dextrorphan / Q000378:metabolism / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007981:Levorphanol / Q000031:analogs & derivatives*; D009019:Morphinans / Q000494:pharmacology*; D016202:N-Methylaspartate; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D000927:Anticonvulsants; D000996:Antitussive Agents; D009019:Morphinans; D003917:Dextrorphan; D007981:Levorphanol; D001224:Aspartic Acid; D016202:N-Methylaspartate; D003915:Dextromethorphan; D015763:2-Amino-5-phosphonovalerate; D014633:Valine