The effects of dihydropyridine calcium channel modulators on pentylenetetrazole convulsions.
The effects of low doses of dihydropyridine (DHP) calcium channel antagonists nimodipine, nifedipine, (-)-R-202-791, and amlodipine, the DHP calcium channel agonist BAY K 8644 were investigated on clonic convulsions to pentylenetetrazole (PTZ) in mice. Nimodipine (2-20 mg/kg) produced a dose-dependent increase in the onset time for convulsions, but did not decrease the number of mice convulsing. Nifedipine, amlodipine (10 mg/kg) and BAY K 8644 (2 mg/kg) also produced an increase in the onset time for convulsions. (-)-R-202-791 (10 mg/kg) was without effect on clonic convulsions to PTZ. BAY K 8644 increased the number of mice dying from tonic-extension convulsions to PTZ. Nimodipine did not affect convulsions elicited by strychnine. Thus, low doses of DHP calcium antagonists possess anticonvulsant properties which are structurally dependent, while DHP calcium channel activators may act to promote convulsions. These observations suggest and support previous evidence that DHP receptors are important modulatory sites for the convulsive state.
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
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O'Neill
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Bolger
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D017311:Amlodipine; D000818:Animals; D000927:Anticonvulsants; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D000927:Anticonvulsants; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C045796:SAN 202791; D009543:Nifedipine