Lynch J J, Rahwan R G, Witiak D T, Cazer F D
Gen Pharmacol. 1983;14(6):571-8. doi: 10.1016/0306-3623(83)90151-9.
Propyl-methylenedioxyindene (pr-MDI) is a coronary dilating and antiarrhythmic calcium antagonist with an intracellular site of action in cardiac tissue, probably involving inhibition of calcium mobilization from the sarcoplasmic reticulum and preservation of mitochondrial structural and functional integrity. Perfusion of isolated guinea-pig hearts with [14C]pr-MDI resulted in negative inotropism, with the time-course of this effect paralleling the uptake of the drug in the whole heart and the time-course of its accumulation in atrial and ventricular tissue. Tissue-to-medium ratios of pr-MDI for both atria and ventricles were high, and washout of the drug from the heart was biexponential. Pr-MDI associated poorly with a cardiac subcellular fraction exhibiting the highest specific activity of sarcolemmal marker enzyme. The highest specific activity of pr-MDI occurred in the cardiac mitochondrial fraction and in a fraction enriched with a putative sarcoplasmic reticular marker, and the accumulation of drug in these fractions was temporally correlated with its negative inotropic action. The results support an intracellular site of action of pr-MDI in cardiac tissue.
丙基 - 亚甲二氧基茚（pr - MDI）是一种冠状动脉扩张和抗心律失常的钙拮抗剂，在心脏组织中具有细胞内作用位点，可能涉及抑制肌浆网钙动员以及维持线粒体结构和功能完整性。用[14C]pr - MDI灌注离体豚鼠心脏导致负性肌力作用，这种作用的时间进程与药物在全心的摄取以及在心房和心室组织中的蓄积时间进程平行。心房和心室的pr - MDI组织与培养基的比率都很高，药物从心脏的洗脱呈双指数形式。pr - MDI与显示肌膜标记酶最高比活性的心脏亚细胞组分结合不佳。pr - MDI的最高比活性出现在心脏线粒体组分和富含假定肌浆网标记物的组分中，药物在这些组分中的蓄积与其负性肌力作用在时间上相关。这些结果支持pr - MDI在心脏组织中的细胞内作用位点。
