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  • Title: Vasodilator mechanism of KB-944, a new calcium antagonist.
    Author: Morita T, Kanazawa T, Ito K, Nose T.
    Journal: Arzneimittelforschung; 1982; 32(9):1043-6. PubMed ID: 6890823.
    Abstract:
    The vasodilator mechanism of diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944) was investigated in anesthetized dogs and isolated aortic and taenia caecum preparations. In anesthetized dogs, the vasodilator effect of KB-944 was not inhibited by propranolol, atropine, diphenhydramine and aminophylline, and did not potentiate the coronary vasodilator action of adenosine. In isolated dog coronary arteries, KB-944 as well as verapamil inhibited the potassium-induced contraction in a concentration-dependent manner. The inhibitory effects of KB-944 and verapamil were overcome by elevating the calcium concentration of the bath solution and a competitive antagonism was found between calcium ions and both compounds. In isolated rabbit aorta, KB-944 (10(-5)--10(-7) mol/l) inhibited potassium-induced contraction in a dose-dependent manner, though KB-944 (3 x 10(-5)--3 x 10(-4) mol/l) slightly inhibited noradrenaline(norepinephrine)-induced contractions. In isolated taenia caecum, KB-944, diltiazem and nifedipine produced a shift to the right of dose-response curves for calcium in a competitive fashion, the pA2 values being 6.84 for KB-944, 6.96 for diltiazem and 9.80 for nifedipine. From these results, it would be that interference with calcium influx contributes to the vasodilator activity of KB-944.
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