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Anticonvulsant effects of some calcium entry blockers in DBA/2 mice
Author(s) -
Sarro G.B.,
Meldrum B.S.,
Nisticó G.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11428.x
Subject(s) - flunarizine , verapamil , dihydropyridine , anticonvulsant , diltiazem , ethosuximide , pharmacology , calcium , antagonist , systemic administration , chemistry , calcium in biology , medicine , endocrinology , epilepsy , biology , in vivo , receptor , microbiology and biotechnology , psychiatry
1 The behavioural and anticonvulsant effects of several drugs acting by various mechanisms on calcium‐channels or affecting intracellular Ca 2+ concentrations were studied after both systemic and intracerebroventricular administration in DBA/2 mice, a strain genetically susceptible to sound‐induced seizures. 2 The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB) in animals placed singly under a perspex dome. 3 Flunarizine and dihydropyridine derivatives, belonging to class I of calcium entry blockers, administered intraperitoneally, were the most potent compounds. 4 Diltiazem, a benzothiazepine derivative belonging to class III, and HA 1004, a calcium antagonist, acting by inhibiting Ca 2+ mobilization from intracellular stores, injected intraperitoneally, were 3–7.6 fold and 5.8–10.7 fold less potent than flunarizine respectively. 5 Verapamil and methoxyverapamil, two phenylalkylamine derivatives, given intraperitoneally, were completely ineffective in preventing sound‐induced seizures in DBA/2 mice. In addition, high doses of verapamil and its methoxyderivative occasionally produced spontaneous tonic‐clonic seizures. 6 After intracerebroventricular administration of the hydrosoluble calcium entry blockers, belonging to different classes, the anticonvulsant effects were similar to those observed after systemic administration. 7 The systemic administration of Bay K 8644, a dihydropyridine analogue, having the ability to stimulate calcium entry into cells produced a dose‐dependent increase in clonic and tonic convulsions and other neurological side effects. 8 The present results strongly support the idea that some Ca 2+ antagonists may be useful in human epilepsy.