Comparison of anticonvulsant effect of ethanol against NMDA-, kainic acid- and picrotoxin-induced convulsions in rats.
The anticonvulsant effect of ethanol against N-methyl-D-aspartic acid-(NMDA), kainic acid-, and picrotoxin-induced convulsions was studied in rats. Ethanol (2 g/kg, ip) offered protection against these agents, and it was most effective against picrotoxin and least effective against kainic acid. MK801, NMDA receptor antagonist, also provided protection against these agents. However, it was most effective against NMDA and least effective against kainic acid. Ineffective doses of MK801 (0.1 mg/kg, ip) and ethanol (0.5 g/kg, ip), when administered concurrently, had a facilitatory anticonvulsant effect, thereby providing protection against mortality following severe convulsions induced by NMDA or picrotoxin, but not against kainic acid. The protective effect of ethanol against NMDA- and kainic acid-induced neurotoxicity, in contrast to picrotoxin-induced toxicity, was not reversed by imidazodiazepine, Ro 15-4513, an ethanol antagonist. Furthermore, Ro 15-4513 did not produce any proconvulsant effect with NMDA or kainic acid. These findings suggested that the anticonvulsant actions of ethanol may be attributed to its ability to antagonize NMDA-mediated excitatory responses and facilitate the GABAergic transmission.
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
S K
SK
Kulkarni
A K
AK
Mehta
M K
MK
Ticku
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D003986:Dibenzocycloheptenes / Q000494:pharmacology / Q000627:therapeutic use; D016291:Dizocilpine Maleate; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology / Q000627:therapeutic use*; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D008297:Male; D016202:N-Methylaspartate; D010852:Picrotoxin / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000517:prevention & control*
D000927:Anticonvulsants; D001224:Aspartic Acid; D003986:Dibenzocycloheptenes; D016291:Dizocilpine Maleate; D000431:Ethanol; D007608:Kainic Acid; D016202:N-Methylaspartate; D010852:Picrotoxin