Endoh M, Yanagisawa T, Morita T, Taira N
J Pharmacol Exp Ther. 1985 Jul;234(1):267-73.
MDL 17,043 [1,3-dihydro-4-methyl-5-[4-(methylthio)-benzoyl]-2H-imidazol-2-one] and AR-L 115 BS [sulmazole, 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b] pyridine] produced substantial positive inotropic effects in a concentration-dependent manner (10(-5) to 10(-3) M) in the isolated canine ventricular trabeculae in the presence of pindolol (3 X 10(-8) M). Both agents exhibited equal potency and intrinsic activity in this preparation. The time to peak tension, relaxation time and total duration of contraction were shortened by MDL 17,043 in a concentration-dependent manner up to the highest concentrations tested (10(-3) M). In contrast, AR-L 115 BS shortened these times in concentrations of 3 X 10(-4) M and lower, but prolonged them in higher concentrations. The positive inotropic effects of MDL 17,043 and AR-L 115 BS were associated with increases in the cyclic AMP levels of the muscles. The time course of the increase in cyclic AMP levels differed for the two drugs. The elevation in cyclic AMP and the positive inotropic effect produced by MDL 17,043 followed a similar time course. By contrast, the rise in the cyclic AMP level became significant only after the positive inotropic effect produced by AR-L 115 BS had reached a steady level. Carbachol, a muscarinic agonist, converted the positive inotropic effect of 10(-3) M MDL 17,043 into a negative inotropic effect, but did not alter the positive inotropic effect of 10(-3) M AR-L 115 BS.(ABSTRACT TRUNCATED AT 250 WORDS)
MDL 17,043 [1,3 - 二氢 - 4 - 甲基 - 5 - [4 - (甲硫基) - 苯甲酰基] - 2H - 咪唑 - 2 - 酮] 和AR - L 115 BS [舒马唑，2 - [(2 - 甲氧基 - 4 - 甲基亚磺酰基)苯基] - 1H - 咪唑并[4,5 - b]吡啶] 在存在吲哚洛尔 (3×10(-8) M) 的情况下，对离体犬心室小梁产生浓度依赖性 (10(-5) 至10(-3) M) 的显著正性肌力作用。在该制剂中，两种药物表现出同等效力和内在活性。MDL 17,043以浓度依赖性方式缩短达峰张力时间、舒张时间和收缩总持续时间，直至所测试的最高浓度 (10(-3) M)。相比之下，AR - L 115 BS在3×10(-4) M及更低浓度下缩短这些时间，但在更高浓度下延长这些时间。MDL 17,043和AR - L 115 BS的正性肌力作用与肌肉中环磷酸腺苷 (cAMP) 水平升高有关。两种药物使cAMP水平升高的时间进程不同。MDL 17,043引起的cAMP水平升高和正性肌力作用遵循相似的时间进程。相比之下，只有在AR - L 115 BS产生的正性肌力作用达到稳定水平后，cAMP水平的升高才变得显著。毒蕈碱激动剂卡巴胆碱将10(-3) M MDL 17,043的正性肌力作用转变为负性肌力作用，但不改变10(-3) M AR - L 115 BS的正性肌力作用。(摘要截短于250字)
