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Differential properties of the optical‐isomers of pranidipine, a 1,4‐dihydropyridine calcium channel modulator
Author(s) -
Hirano Takahiro,
Mori Toyoki,
Kido Masaru,
Toide Kiyotaka,
Ohura Makoto,
Fujiki Hiroyuki,
Orito Kensuke,
Yoshida Kenji,
Ikezono Katsumi,
Sumida Takumi,
Nakayama Natsuki,
Yabuuchi Youichi
Publication year - 1999
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1999.tb00376.x
Subject(s) - chemistry , dihydropyridine , enantiomer , calcium channel , calcium , stereochemistry , voltage dependent calcium channel , contraction (grammar) , extracellular , biophysics , biochemistry , endocrinology , organic chemistry , biology , medicine
— 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 Ca 2+ . The apparent pA 2 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 Ca 2+ 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’.