Assessment of Ca(2+)-antagonistic effect of SM-6586 and its isomers, novel 1,4-dihydropyridine derivatives, by radioligand binding assay.
The Ca(2+)-antagonistic effects of the 1,4-dihydropyridine derivative (+/-)SM-6586 and its optical isomers were compared with those of its two derivatives ((+/-)SM-7297 and (+/-)SM-7548) and other Ca(2+)-antagonists using a radioligand binding assay. The Ca(2+)-antagonistic effects of the optical isomers of SM-6586 were in the order of (+) greater than (+/-) greater than (-)SM-6586 in both rat brain and heart. The pKi value of (+)SM-6586 was comparable to those of nimodipine, nicardipine, nifedipine and nitrendipine. The pA2 value for (+)SM-6586 was the highest among the SM-6586 isomers, thus suggesting that (+)SM-6586 has a potent Ca(2+)-antagonistic effect.
Kinami
J
J
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Qu
Y L
YL
Tsuchihashi
H
H
Nagatomo
T
T
Maniwa
T
T
Miyagishi
A
A
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000737:chemistry; D010069:Oxadiazoles / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D013895:Thoracic Arteries / Q000187:drug effects; D014316:Tritium
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D010069:Oxadiazoles; D014316:Tritium; C075861:SM 6586