Pharmacology of the new calcium antagonist isradipine and its metabolites
1988; Elsevier BV; Volume: 84; Issue: 3 Linguagem: Inglês
10.1016/0002-9343(88)90182-9
ISSN1555-7162
Autores Tópico(s)Analytical Methods in Pharmaceuticals
ResumoThe pharmacologic properties of isradipine (PN200-110), its enantiomers, and its major metabolites occurring in human blood are reviewed. Isradipine is a dihydropyridine derivative with a high specific and a low nonspecific affinity to the dihydropyridine binding site of the L-type calcium channel. The nonspecific receptor-operated calcium channel of rabbit aorta is not blocked, but receptor-operated channels in resistance vessels are blocked, which implies that they resemble L-channels. In the heart, isradipine acts selectively on the sinus node but not on the atrioventricular node. Also, its cardiodepressant effect is minimal. The cause of this selectivity is not known; differences between the channels, or a different electrophysiologic behavior of these tissues, might account for it. The pharmacodynamic activity resides in the (+)enantiomer that is on the order of 150 times more active than the (−)enantiomer. The major metabolites found in human blood were tested for evidence of calcium channel blockade. None of them had a relevant calcium antagonist-like activity in vitro. Four of the five metabolites were also tested for their effect on the cardiovascular system in anesthetized cats, and all four were found to be inactive. Pharmacodynamic effects of isradipine are therefore attributable entirely to isradipine itself.
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