Involvement of a GABAergic mechanism in the pharmacologic action of phenytoin.
In vivo interactions between phenytoin (PHT) and baclofen (a GABAb receptor agonist) or PHT and progabide (a GABAa receptor agonist) were investigated by the rotorod minimal neurotoxicity test and maximal electroshock seizure (MES) test. The combination of PHT and baclofen produced an additive effect by the rotorod test, whereas the combination of PHT and progabide elicited a supra-additive (synergistic) effect. The median minimal neurotoxic dose of baclofen augmented the anti-MES activity of PHT. The combination of PHT and progabide induced a supra-additive effect by the MES test. These results imply that GABAa receptors are involved in both the minimal neurotoxicity and anti-MES activity of PHT.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000633:toxicity; D001418:Baclofen / Q000494:pharmacology / Q000633:toxicity; D004597:Electroshock; D008297:Male; D051379:Mice; D010672:Phenytoin / Q000494:pharmacology* / Q000633:toxicity; D004856:Postural Balance / Q000187:drug effects; D012640:Seizures / Q000517:prevention & control; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology* / Q000633:toxicity
D000927:Anticonvulsants; C017985:progabide; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D001418:Baclofen