Calcium Entry Blocking Activity of Dilazep in Dog Coronary Artery

Calcium entry blocking activities of adenosine and its potentiating compounds (dipyridamole, lidoflazine and dilazep) were studied in potassium (100 mmol/l) depolarized, dog, large coronary artery strips, in comparison to nifedipine, verapamil and diltiazem. Apparent pA2 values were calculated by using concentration-response curves for calcium before and 30 min after the addition of each dilator drug. The order of potency (using both pA2 and IC50 values) for the calcium entry blocking effect was: nifedipine greater than verapamil greater than diltiazem greater than lidoflazine greater than dilazep. Dipyridamole and adenosine had negligible calcium entry blocking activities (about 10,000 times less potent than verapamil). The calcium entry blocking activity of verapamil (using pA2 values) was 39.8 times less potent than nifedipine, and 3.6, 21.4 and 97.7 times more potent than diltiazem, lidoflazine and dilazep, respectively. The maximum relaxations induced by adenosine (3.7 X 10(-4) mol/l) and dipyridamole (5 X 10(-5) mol/l) were less than 20% that of 3 X 10(-4) mol/l papaverine. However, the other test drugs caused 80-90% relaxation under similar conditions. The relaxing effect of adenosine was inhibited by 8-phenyltheophylline (adenosine receptor antagonist) and potentiated by EHNA (an adenosine deaminase inhibitor), while dilazep-induced relaxation was not affected by these drugs. These findings suggest that the calcium entry blocking effect of dilazep in dog, large coronary artery strips is not mediated through adenosine.