Effects of diltiazem in convulsive states differ from those previously reported for dihydropyridine calcium channel antagonists.
Unlike the dihydropyridine calcium channel antagonists studied previously, the benzothiazepine calcium channel antagonist, diltiazem, increased the incidence of convulsions caused by bicuculline, N-methyl-DL-aspartate or 4-aminopyridine. However, the latencies to convulsions were also increased. Diltiazem increased the ratings of convulsive behaviour on handling after intraperitoneal administration of bicuculline, or pentylenetetrazol and after the calcium channel activator, Bay K 8644, administered ICV. When the binding of the dihydropyridine, [3H]-nitrendipine in the CNS was measured in vivo, this was increased by diltiazem. This compound therefore showed a different pattern of interaction with convulsant drugs then that previously demonstrated for other calcium channel antagonists, appearing to possess both pro- and anticonvulsant actions, and a different pattern of interaction with the dihydropyridine receptor complex.
Watson
W P
WP
Pharmacology Department, Medical School, University Walk, Bristol, UK.
Little
H J
HJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003292:Convulsants / Q000008:administration & dosage / Q000494:pharmacology; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009568:Nitrendipine / Q000493:pharmacokinetics; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology
D002121:Calcium Channel Blockers; D003292:Convulsants; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D004110:Diltiazem