Effects of dextromethorphan, a nonopioid antitussive, on development and expression of amygdaloid kindled seizures.
The effects of dextromethorphan (DM), a nonopioid antitussive and a functional N-methyl-D-aspartate (NMDA) antagonist, on expression and development of amygdaloid kindled seizures were examined. The maximum anticonvulsant effect of DM (30 mg/kg) on fully kindled seizures appeared within 30 min of administration and lasted for at least 2 h. DM decreased, in a dose-dependent manner [10-70 mg/kg, intraperitoneally (i.p.)], the severity of kindled seizures 30 min after injection, but the estimated ED50 was 3 times higher than the previously reported value for maximal electroshock convulsions. Furthermore, the high dose (70 mg/kg), while suppressing kindled seizures, produced myoclonus which coincided with EEG spike activity in the amygdala and the cortex. When tested on the development of kindling, 30 mg/kg DM retarded the growth of afterdischarge in the amygdala and the cortex, but had no effect on the development of behavioral seizures. DM 60 mg/kg accelerated development of kindling and produced spontaneous seizures. These results indicate that DM, unlike other NMDA antagonists, has a narrow therapeutic window as an anticonvulsant on kindled seizures and that higher doses may potentiate the kindling process.
Department of Psychology, University of Otago, Dunedin, New Zealand.
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Takazawa
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Anderson
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WC
Abraham
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003915:Dextromethorphan / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D007696:Kindling, Neurologic / Q000187:drug effects; D007981:Levorphanol / Q000031:analogs & derivatives*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012146:Rest; D012640:Seizures / Q000503:physiopathology*; D013997:Time Factors
D000996:Antitussive Agents; D007981:Levorphanol; D003915:Dextromethorphan