title: Differential properties of the optical-isomers of pranidipine, a 1,4-dihydropyridine calcium channel modulator.
abstract: 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 microg/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'.
authors.affiliation: 2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Kido
authors.forename: K
authors.initials: K
authors.lastname: Toide
authors.forename: M
authors.initials: M
authors.lastname: Ohura
authors.forename: H
authors.initials: H
authors.lastname: Fujiki
authors.forename: K
authors.initials: K
authors.lastname: Orito
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Ikezono
authors.forename: T
authors.initials: T
authors.lastname: Sumida
authors.forename: N
authors.initials: N
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Yabuuchi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C048161:pranidipine