Interactions of pentobarbital and phenobarbital with GABAergic drugs against chemoconvulsants in rats.
Pentobarbital and phenobarbital exhibited anticonvulsant effects against picrotoxin (10 mg/kg, IP) as well as against strychnine (4 mg/kg, IP). Pentobarbital was also effective against bicuculline whereas only hypnotic doses of phenobarbital provided some protection against bicuculline- (8 mg/kg, IP) induced convulsions. Diazepam as well as THIP, but not baclofen, were also effective against all the three chemoconvulsants. Baclofen or subeffective doses of diazepam or THIP, when combined with subeffective dose of pentobarbital exhibited anticonvulsant activity against all the chemoconvulsants studied. On the other hand, a combination of subeffective doses of these agents with subeffective doses of phenobarbital provided protection only against picrotoxin and strychnine. These observations indicate that pentobarbital is quite effective against convulsions caused by agents acting at picrotoxin site, GABAA receptor or glycine receptor whereas phenobarbital is effective only against agents acting at picrotoxin site and glycine receptor, and is very weak anticonvulsant against agents causing blockade of GABAA receptors. Furthermore, activation of GABAA receptors or benzodiazepine receptors also provide protection against agents acting at GABAergic system or glycine receptors. On the contrary, activation of only GABAB receptors is inadequate to provide the protective effect. However, the activation of GABAA as well as GABAB receptors facilitate the anticonvulsant effect of both the barbiturates. Furthermore, pentobarbital, but not phenobarbital, facilitates the anticonvulsant effect of benzodiazepines against chemoconvulsants acting at GABAergic site or glycine receptors.
Mehta
A K
AK
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
Ticku
M K
MK
D000818:Animals; D000927:Anticonvulsants; D001418:Baclofen / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology* / Q000633:toxicity; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012640:Seizures / Q000503:physiopathology; D013331:Strychnine / Q000494:pharmacology
D000927:Anticonvulsants; D001418:Baclofen; D001640:Bicuculline; D003292:Convulsants; D003975:Diazepam; D007555:Isoxazoles; D010424:Pentobarbital; D010634:Phenobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; D013331:Strychnine; C015542:gaboxadol