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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 &gt; or = nisoldipine &gt; nifedipine, whereas in high K(+)-induced contraction, it was nisoldipine &gt; efonidipine &gt; 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.

Spasmolytic Effect of Efonidipine Hydrochloride in Isolated Canine Coronary Artery: Comparison with the Effects of Nifedipine and Nisoldipine.