Spasmolytic effect of efonidipine hydrochloride in isolated canine coronary artery: comparison with the effects of nifedipine and nisoldipine.
Spasmolytic effects of efonidipine hydrochloride (efonidipine) on high K(+)-, U46619- and 3,4-diaminopyridine (3,4-DAP)-induced contractions were evaluated in isolated canine coronary, artery, and were compared with the effects of nifedipine and nisoldipine. Efonidipine (0.3-30 nM), nifedipine (1-300 nM) and nisoldipine (0.1-100 nM) each relaxed the contractions induced by high K+ and U46619. However, relaxation produced by efonidipine was slower than that produced by nifedipine or nisoldipine. The rank order of potency of these drugs for U46619-induced contraction was efonidipine > or = nisoldipine > nifedipine, whereas in high K(+)-induced contraction, it was nisoldipine > efonidipine > nifedipine. Thus, the relaxing effect of efonidipine on U46619-induced contraction appeared to be more potent than its effect on high K(+)-induced contractions, when compared with the effects of nifedipine and nisoldipine. These three drugs also suppressed 3,4-DAP-induced rhythmic contractions. However, a marked time-dependent increase in potency was only observed for efonidipine, and was similar to its time-dependent effect on high K(+)- and U46619-induced contractions. Efonidipine did not change the contraction cycle length whilst suppressing the peak contractions. On the other hand, lower concentration of nifedipine at 3 nM and nisoldipine at 1 nM significantly shortened the cycle length. These results suggest that efonidipine may be an effective agent for the treatment of angina pectoris. The high potency of efonidipine for U46619-induced contractions will provide some advantages in the clinical use of this compound on thromboxane A2-mediated coronary vasoconstriction.
Jin
H
H
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Sato
R
R
Higashino
R
R
Fukuda
Y
Y
Kurimoto
T
T
Tamaki
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D066298:In Vitro Techniques; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C066425:efonidipine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015761:4-Aminopyridine; D000077770:Amifampridine; D011188:Potassium