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The pharmacological properties of YM-15430-1 and its stereoisomers (YM-15430-2, YM-15430-3 and YM-15430-4) were evaluated in in vitro experiments. In the rabbit isolated aorta, all compounds antagonized the CaCl2-induced contraction with a negative logarithm of the dissociation constant in calcium antagonism of 8.51, 7.13, 8.68 and 7.16, respectively. In the rat isolated right atrium, YM-15430-1 produced a competitive antagonism of the isoprenaline-induced tachycardia with a pA2 value of 7.59. YM-15430-2, YM-15430-3 and YM-15430-4 also antagonized the isoprenaline-induced tachycardia, with pA2 values of 7.91, 7.09 and 6.24, respectively. Because it was the most active of the 4 stereoisomers, YM-15430-1 was particularly studied. YM-15430-1 showed an about 100-fold greater selectivity for beta 1- than for beta 2-adrenoceptors, and had no intrinsic sympathomimetic activity. These results suggest that YM-15430-1 is a hybrid compound which combines calcium entry-blocking and selective beta 1-adrenoceptor-blocking activities in one molecule.

Citation

K Shibasaki, W Uchida, Y Shirai, O Inagaki, M Asano, T Takenaka. Pharmacological properties of YM-15430-1, a 1,4-dihydropyridine derivative with beta 1-adrenoceptor-blocking activity. Archives internationales de pharmacodynamie et de thérapie. 1994 Sep-Oct;328(2):213-24

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PMID: 7710306

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