Effects of some convulsant agents on the protective activity of topiramate against maximal electroshock-induced seizures in mice.
The anticonvulsant activity of topiramate combined with some convulsant agents (bicuculline--BIC, N-methyl-D-aspartate--NMDA, and kainic acid--KA), given at subconvulsive doses, was evaluated in the maximal electroshock (MES)-test in mice. BIC (1.5 mg/kg), KA (10 mg/kg) and NMDA (50 mg/kg) significantly decreased the anticonvulsant activity of topiramate raising its ED(50) from 76.2 mg/kg to 135, 102, and 107 mg/kg, respectively. BIC (0.75 mg/kg) and KA (5 mg/kg) did not alter the protective activity of topiramate in the MES-test. Moreover, topiramate injected alone (up to 135 mg/kg) did not affect motor performance and long-term memory of animals tested in the chimney and passive avoidance tests, respectively. In contrast, combinations of topiramate with BIC (1.5 mg/kg), NMDA (50 mg/kg) or KA (10 mg/kg) considerably disturbed long-term memory in mice. Additionally, co-administration of topiramate with KA (10 mg/kg) or BIC (1.5 mg/kg) significantly impaired motor performance, whereas topiramate co-administered with NMDA (50 mg/kg) had no impact on motor coordination in mice. None of the studied convulsants affected the free plasma concentration of topiramate assayed with immunofluorescence method. The results of this study seem to indicate the expression of the anticonvulsant activity of topiramate is dependent on all ionotropic glutamate and GABAA receptor-mediated events.
Department of Pharmacology and Toxicology, Medical University of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland.
Mariusz J
MJ
Swiader
Jarogniew J
JJ
Łuszczki
Anna
A
Zwolan
Marian
M
Wielosz
Stainsław J
SJ
Czuczwar
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D004347:Drug Interactions; D004597:Electroshock; D005632:Fructose / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects; D012640:Seizures / Q000517:prevention & control*; D000077236:Topiramate
D000927:Anticonvulsants; D003292:Convulsants; D011963:Receptors, GABA-A; D000077236:Topiramate; D005632:Fructose; D016202:N-Methylaspartate; D007608:Kainic Acid; D001640:Bicuculline