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 w ere evaluated in isolated canine coronary artery, and were compared wi th the effects of nifedipine and nisoldipine, Efonidipine (0.3-30 nM), nifedipine (1-300 nM) and nisoldipine (0.1-100 nM) each relaxed the c ontractions induced by high K+ and U46619. However, relaxation produce d by efonidipine was slower than that produced by nifedipine or nisold ipine. The rank order of potency of these drugs for U46619-induced con traction was efonidipine greater than or equal to nisoldipine > nifedi pine, whereas in high K+-induced contraction, it was nisoldipine > efo nidipine > nifedipine. Thus, the relaxing effect of efonidipine on U46 619-induced contraction appeared to be more potent than its effect on high K+-induced contractions, when compared with the effects of nifedi pine and nisoldipine. These three drugs also suppressed 3,4-DAP-induce d 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 U466L9-induced contractions, Efonidi pine did not change the contraction cycle length whilst suppressing th e peak contractions, On the other hand, lo,ver concentration of nifedi pine at 3 nM and nisoldipine at 1 nM significantly shortened the cycle length, These results suggest that efonidipine may be an effective ag ent for the treatment of angina pectoris. The high potency of efonidip ine for U46619-induced contractions, will provide some advantages in t he clinical use of this compound on thromboxane A(2)-mediated coronary vasoconstriction.