Anticonvulsant action of chlormethiazole is prevented by subconvulsive amounts of strychnine and aminophylline but not by bicuculline and picrotoxin.
The anticonvulsant action of chlormethiazole was evaluated with the use of subthreshold doses of convulsants affecting the purinergic, glycinergic and gamma-aminobutyric acid (GABA)-mediated transmission, i.e. aminophylline, strychnine, bicuculline and picrotoxin in the model of generalized tonic-clonic convulsions. Chlormethiazole protected mice against maximal electroshock-induced seizures with an ED50 of 130.8 mg/kg. Aminophylline (100 mg/kg) and strychnine (0.4 mg/kg) reversed the protective action of chlormethiazole against electroconvulsions raising the ED50 values of this drug to 218.6 and 208.6 mg/kg, respectively. In contrast, GABA antagonists, bicuculline and picrotoxin, neither affected the protection provided by chlormethiazole nor did they alter the protective activity of valproate, phenobarbital, diphenylhydantoin and carbamazepine against electroconvulsions. Our results indicate that (a) the anticonvulsant activity of chlormethiazole might be related to its interaction with strychnine-sensitive glycinergic as well as purinergic neurotransmission, (b) purinergic and strychnine-sensitive glycinergic events contribute more prominently than GABAergic ones to the anticonvulsant activity of the drugs providing protection against maximal electroshock-induced convulsions.
Pilip
S
S
Department of Pharmacology and Toxicology, Medical University, Lublin, Poland.
Urbańska
E M
EM
Swiader
M
M
Włodarczyk
D
D
Kleinrok
Z
Z
Czuczwar
S J
SJ
Turski
W A
WA
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology*; D002719:Chlormethiazole / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D004597:Electroshock; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051379:Mice; D010852:Picrotoxin / Q000494:pharmacology*; D013331:Strychnine / Q000494:pharmacology*
D000628:Aminophylline; D000927:Anticonvulsants; D001640:Bicuculline; D002719:Chlormethiazole; D003292:Convulsants; D010852:Picrotoxin; D013331:Strychnine