Anticonvulsant profile of the dihydropyridine calcium channel antagonists, nitrendipine and nimodipine.
The effects of the dihydropyridine calcium channel antagonists, nitrendipine and nimodipine, on convulsions produced by different mechanisms have been studied in rats. Nitrendipine and nimodipine significantly raised the thresholds to pentylenetetrazol for up to six hours after their injection. The calcium channel agonist, BAY K 8644, lowered the convulsion threshold to pentylenetetrazol and antagonised the effects of nitrendipine. In contrast, the severity of seizures produced by N-methyl-dl-aspartate (NMA) was increased by nitrendipine. BAY K 8644 also slightly increased the effects of NMA. Nimodipine and nitrendipine caused small, but significant, increases in the threshold pressures for the convulsions caused by raising the atmospheric pressure with helium gas. The compounds had no effect on strychnine convulsions. The conclusion is that the calcium channel antagonists are anticonvulsant against only certain types of convulsions, such as pentylenetetrazol and high pressure (and ethanol withdrawal, reported previously). Others may be increased, such as NMA seizures, or unaffected, such as strychnine-induced convulsions.
Dolin
S J
SJ
Department of Anaesthesia, Addenbrooke's Hospital, Cambridge, U.K.
Hunter
A B
AB
Halsey
M J
MJ
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; D000927:Anticonvulsants; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D001274:Atmospheric Pressure; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004594:Electrophysiology; D008297:Male; D016202:N-Methylaspartate; D009553:Nimodipine / Q000494:pharmacology*; D009568:Nitrendipine / Q000494:pharmacology*; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013331:Strychnine / Q000037:antagonists & inhibitors
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D001224:Aspartic Acid; D009553:Nimodipine; D016202:N-Methylaspartate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D013331:Strychnine; D010433:Pentylenetetrazole