Differential properties of the optical-isomers of pranidipine, a 1,4-dihydropyridine calcium channel modulator

— Pranidipine is an optically‐active 1,4‐dihydropyridine (DHP) voltage‐dependent L‐type calcium channel inhibitor. Certain enantiomeric pairs display opposite effects, i.e., inhibition and activation of the calcium channel while others exhibit the same qualitative actions. We investigated pranidipine, a new DHP, using a paradigm of vascular smooth muscle reactivity. In isolated rat aorta, depolarized with 80 mM KCl, both isomers of pranidipine caused a right‐ward shift of the concentration‐contraction curves for extracellular Ca2+. The apparent pA2 values of the S‐isomer and R‐isomer were 10.03 and 8.36, respectively, providing evidence that the calcium channel blocking action of the S‐isomer was 50 times more potent than that of the R‐isomer. Antihypertensive actions of these two isomers studied in pentobarbital‐anaesthetized spontaneously hypertensive rats, revealed that the S‐isomer, at doses of 3–30 μg/kg i.v. decreased blood pressure in a dose‐dependent manner, while the R‐isomer had no effect on blood pressure at those doses. We conclude that the pair of enantiomers of pranidipine qualitatively display the same Ca2+channel blocking action and that neither isomer exhibits Bay K 8644‐like activation. Pranidipine may be useful in studies on the architecture of the DHP receptor ‘pocket’.