Vasodilator mechanism of KB-944, a new calcium antagonist.
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.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology*; D014665:Vasodilator Agents; D014700:Verapamil / Q000494:pharmacology
D052160:Benzothiazoles; D002121:Calcium Channel Blockers; D013844:Thiazoles; D014665:Vasodilator Agents; D014700:Verapamil; C035950:fosfedil; D004110:Diltiazem; D009543:Nifedipine; D000241:Adenosine; D002122:Calcium Chloride; D011188:Potassium