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• W1990520002 abstract "A series of dihydropyridine derivatives has been evaluated for calcium channel agonist activity using reversal of nisoldipine‐induced inhibition of beating of aggregates of embryonic chick myocytes. This test appears to be specific for calcium channel agonists since isoprenaline and cardiac glycosides are inactive. RS 30026 was the most potent of the series, was significantly more potent than CGP 28392 and of similar potency to Bay K 8644 (pEC 50 = 7.45, 6.16 and 7.20, respectively). RS 30026 increased edge movement of individual aggregates, in the absence of nisoldipine, by 50% at 2n m . Compounds were also evaluated for their effects on guinea‐pig papillary muscle and porcine coronary artery rings. RS 30026 displayed positive inotropism at concentrations between 10 −9 and 10 −6 m (pEC 200 = 8.21), but was a much more powerful inotrope than Bay K 8644, increasing contractility to 1300% of control at 10 −6 m (compared to 350% of control for Bay K 8644). RS 30026 caused vasoconstriction at concentrations between 10 −10 and 10 −7 m . Calcium channel currents in single embryonic chick myocytes were recorded by whole‐cell voltage clamp techniques. RS 30026 (100 n m ‐500 n m ) produced large increases in peak current amplitude and shifted the voltage for threshold and maximal currents to more negative values. RS 30026 (500 n m ) also produced large increases in the inward tail currents evoked upon repolarization. The effects of Bay K 8644 (50 and 500 n m ) were much less marked. Analysis of the activation characteristics of currents showed parallel shifts in the activation curve to more negative potentials in the presence of 50 n m Bay K 8644, with a much smaller shift in the presence of 500 n m Bay K 8644. RS 30026 (100 and 500 n m ) caused concentration‐dependent shifts in the activation of the calcium channel currents with an increase of the slope of the curve. RS 30026 appears to be the most potent and effective calcium channel agonist described to date." @default.
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• W1990520002 date "1990-04-01" @default.
• W1990520002 modified "2023-10-17" @default.
• W1990520002 title "RS 30026: a potent and effective calcium channel agonist" @default.
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• W1990520002 doi "https://doi.org/10.1111/j.1476-5381.1990.tb12990.x" @default.
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