Calcium Channel Blocking Properties of SM-6586 in Rat Heart and Brain as Assessed by Radioligand Binding Assay.
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概要
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The interaction of SM-6586 (methyl 1, 4-dihydro-2, 6-dimethyl-3-{3-(<I>N</I>-benzyl-<I>N</I>-methyl-aminomethyl)-1, 2, 4-oxadiazolyl-5-yl}-4-(3-nitrophenyl)pyridine-5-carboxylate) with the specific binding of <SUP>3</SUP>H-PN200-110 to rat heart and brain membranes was characterized and compared with those of other Ca<SUP>2+</SUP> antagonists. The blockade of <SUP>3</SUP>H-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 inhibited 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.
- 公益社団法人 日本薬理学会の論文
著者
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Miyagishi Akira
Research Center Sumitomo Pharmaceuticals Co. Ltd
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Nagatomo Takafumi
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Niigata University Of Pharmacy And App
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Maniwa Takashi
Research Laboratories, Sumitomo Pharmaceuticals Co. Ltd.
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Qu Ying-Li
Department of Pharmacology, Niigata College of Pharmacy
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Sugiyama Kentaro
Department of Pharmacology, Niigata College of Pharmacy
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