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.
Leander
J D
JD
Central Nervous System Research, Eli Lilly and Company, Indianapolis, IN 46285.
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D000996:Antitussive Agents / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D003517:Cyclopentanes / Q000627:therapeutic use*; D003915:Dextromethorphan / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007981:Levorphanol / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D016202:N-Methylaspartate; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D000927:Anticonvulsants; D000996:Antitussive Agents; D003517:Cyclopentanes; D007981:Levorphanol; D001224:Aspartic Acid; C018861:carbetapentane; D016202:N-Methylaspartate; D003915:Dextromethorphan