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-depend ent L-type calcium channel inhibitor. Certain enantiomeric pairs display op posite effects, i.e., inhibition and activation of the calcium channel whil e others exhibit the same qualitative actions. We investigated pranidipine, a new DHP, using a paradigm of vascular smooth muscle reactivity. In isola ted rat aorta, depolarized with 80 mM KCl, both isomers of pranidipine caus ed a right-ward shift of the concentration-contraction curves for extracell ular Ca2+. The apparent pA(2) values of the S-isomer and R-isomer were 10.0 3 and 8.36, respectively, providing evidence that the calcium channel block ing action of the S-isomer was 50 times more potent than that of the R-isom er. Antihypertensive actions of these two isomers studied in pentobarbital- anaesthetized spontaneously hypertensive rats, revealed that the S-isomer, at doses of 3-30 mu g/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 displ ay the same Ca2+ channel blocking action and that neither isomer exhibits B ay K 8644-like activation. Pranidipine may be useful in studies on the arch itecture of the DHP receptor 'pocket'. (C) 1999 Editions scientifiques et m edicales Elsevier SAS.