title: Inhibitory effects of efonidipine hydrochloride on contraction induced by several vasoconstrictors in porcine coronary artery: comparison with effects of nifedipine and nisoldipine.
abstract: We studied the effects of efonidipine hydrochloride (efonidipine), a 1,4-dihydropyridine derivative, on contractions induced by high-K+ solution (high K+), serotonin (5-HT), U46619, which is a stable analog of thromboxane A2, and endothelin-1 (ET-1) in comparison with those of nifedipine and nisoldipine in porcine coronary arteries. The effects of the drugs were compared after 1- and 3-h incubations. Efonidipine, nifedipine, and nisoldipine each inhibited the contractions induced by these vasoconstrictors. The inhibition of high-K(+)- and 5-HT-induced contractions by efonidipine, but not by nifedipine and nisoldipine, increased when the incubation time was prolonged, whereas the inhibition of U46619- and ET-1-induced contractions was not altered. The potency of efonidipine on U46619- and ET-1-induced contractions was greater than that of nifedipine and equivalent to that of nisoldipine. Thus the inhibitory effect of efonidipine on U46619- and ET-1-induced contractions seems to be stronger than its effects on high-K(+)- or 5-HT-induced contractions, in contrast to the effects of other dihydropyridines. In an additional series of experiments, efonidipine did not inhibit U46619-induced contractions in Ca2(+)-free solution or in the presence of nifedipine. Moreover, efonidipine did not inhibit the specific binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to porcine coronary arterial membrane. Therefore we think that the inhibitory effect of efonidipine on contractions induced by vasoconstrictors was caused by blockade of Ca2+ influx through L-type Ca2+ channels. However, some unknown mechanism(s) in addition to this effect on Ca2+ channels may contribute to the effect of efonidipine on U46619- and ET-1-induced contractions.
authors.affiliation: Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Higashino
authors.forename: R
authors.initials: R
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Jin
authors.forename: N
authors.initials: N
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuta
authors.forename: T
authors.initials: T
authors.lastname: Kurimoto
authors.forename: H
authors.initials: H
authors.lastname: Tamaki
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D015737:Nisoldipine / Q000494:pharmacology*; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D019332:Endothelin-1; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D012701:Serotonin; C066425:efonidipine; D015737:Nisoldipine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009543:Nifedipine; D011188:Potassium