Evaluation of dextromethorphan and carbetapentane as anticonvulsants and N-methyl-D-aspartic acid antagonists in mice.

Two antitussives, dextromethorphan and carbetapentane, which have been reported to bind to a common binding site in brain tissue and produce anticonvulsant effects in rats, were evaluated for their anticonvulsant effects against maximal electroshock-induced seizures, for their neurological impairing effects on the horizontal screen test, and their protective effects against N-methyl-D-aspartic acid (NMDA)-induced lethality in mice. Both compounds protected animals against maximal electroshock-induced seizures in a dose-related fashion after either intraperitoneal or oral administration. The neurologically impairing doses were approximately 1.5 times the anticonvulsant doses. As a function of dose, dextromethorphan, but not carbetapentane, protected mice from NMDA-induced lethality. Since carbetapentane had an anticonvulsant action without protecting against NMDA-induced lethality, these data support the hypothesis that dextromethorphan and carbetapentane may have a common anticonvulsant action separate from the phencyclidine-like, NMDA-antagonist action which only dextromethorphan exhibits.