title: Calcium channel blocking properties of SM-6586 in rat heart and brain as assessed by radioligand binding assay.
abstract: The interaction of SM-6586 (methyl 1,4-dihydro-2,6-dimethyl-3-[3-(N-benzyl-N-methyl-aminomethyl)-1,2,4- oxadiazolyl-5-yl]-4-(3-nitrophenyl)pyridine-5-carboxylate) with the specific binding of 3H-PN200-110 to rat heart and brain membranes was characterized and compared with those of other Ca2+ antagonists. The blockade of 3H-PN200-110 binding sites induced by nifedipine, nitrendipine and nimodipine was reversed by washing, whereas the blockade by SM-6586 was not readily reversed under these conditions. No significant difference was found in irreversibility between SM-6586 enantiomers. When rat aortic strips were pretreated with SM-6586, the contractions induced by 50 mM KCl were inhibits even though SM-6586 was not present in the extracellular medium. This residual inhibitory effect was much stronger than that of nicardipine. The inhibition of KCl-induced contractions by nifedipine and nitrendipine was easily reversed by washing. Thus, we suggest that (+)SM-6586 is a novel 1,4-dihydropyridine derivative having a very slow rate of dissociation from the binding site. This property may explain its long-lasting antihypertensive effect.
authors.affiliation: Department of Pharmacology, Niigata College of Pharmacy, Japan.
authors.forename: Y L
authors.initials: YL
authors.lastname: Qu
authors.forename: K
authors.initials: K
authors.lastname: Sugiyama
authors.forename: T
authors.initials: T
authors.lastname: Nagatomo
authors.forename: T
authors.initials: T
authors.lastname: Maniwa
authors.forename: A
authors.initials: A
authors.lastname: Miyagishi
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D017275:Isradipine / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology*; D011188:Potassium; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D010069:Oxadiazoles; D014316:Tritium; C075861:SM 6586; D011188:Potassium; D017275:Isradipine