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A Further Study of the Vasodilator and Negative Inotropic Mechanisms of Action of Nicorandil and Its Congeners in the Canine Heart

A Further Study of the Vasodilator and Negative Inotropic Mechanisms of Action of Nicorandil and Its Congeners in the Canine Heart

K Satoh, K Orito, F Yoneyama, N Taira

Cardiovasc Drugs Ther. 1994 Apr;8(2):227-34.

PMID: 7918135

Abstract:

The vasodilator and negative inotropic mechanisms of action of nicorandil and its congeners (SG-209, SG-103, and SG-86) were investigated in isolated canine papillary muscle preparations cross-circulated through the anterior septal artery with support dogs. SG-209, SG-103, and SG-86 were obtained by replacement of the nitroxyl group of nicorandil by acetoxyl, nicotinoyloxyl, and hydroxyl groups, respectively. Nicorandil (0.03-10 mumol), SG-209 (0.1-10 mumol), SG-103 (1-30 mumol), and SG-86 (3-100 mumol) all produced an increase in coronary blood flow through the anterior septal artery. Both nicorandil and SG-209 produced a near-maximal increase in coronary blood flow, the latter being about 5.5 times less potent than the former. SG-103 and SG-86 were far less potent than SG-209 in that order. The vasodilator actions of nicorandil and SG-209 were antagonized by glibenclamide given IV to support dogs, but those of SG-103 and SG-86 were not. The pKB values of glibenclamide were 6.34 toward nicorandil and 6.49 toward SG-209. Developed tension of the papillary muscle was reduced by nicorandil, SG-209, and SG-103, but not by SG-86. In this respect SG-209 was about 4.7 times less potent than nicorandil, and SG-103 was much less potent than SG-209. The negative inotropic effects of nicorandil and SG-209 were antagonized by glibenclamide, but that of SG-103 was not.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP83440033	SG-209		83440-03-3	Price

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