The antiseizure activity of dihydropyridine calcium channel antagonists in the conscious rat.
By using a rat seizure model, a comparison of the antiseizure activity of 12 dihydropyridine calcium channel antagonists (administered i.c.v.) to their binding affinities for the neuronal site known to regulate L-type calcium channels was made. For these dihydropyridine calcium channel antagonists a correlation between physiologic activity and binding affinities would provide evidence that these agents exert their antiseizure actions via a mechanism involving a binding site that regulates L-type neuronal calcium channels. Despite i.c.v. administration, a parallel in antiseizure activity and binding affinities could not be demonstrated precisely, suggesting that the dihydropyridines may be exerting their antiseizure activity by more than just simple neuronal calcium channel blockade.
Morón
M A
MA
Department of Pharmacology, Mayo Clinic Rochester, Minnesota.
Stevens
C W
CW
Yaksh
T L
TL
D000818:Animals; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000627:therapeutic use*; D004569:Electroencephalography; D007276:Injections, Intraventricular; D008297:Male; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013329:Structure-Activity Relationship
D002120:Calcium Channel Agonists; D004095:Dihydropyridines; D010433:Pentylenetetrazole