Labrid C
Presse Med. 1986 Oct 16;15(35):1754-7.
In contrast with the classical anti-anginal drugs, trimetazidine appears to be a very specific treatment, especially to the ischaemic cell. Whereas beta-blockers, nitrates and calcium antagonists all act outside the real ischaemic area (on peripheral veins or arteries, coronary vessels, whole heart muscle contractility, sinus node, endo-epicardial blood flow ratio, etc...) trimetazidine is only efficient on the ischaemia-induced loss of membrane functions and its consequences. The disturbance of tissue oxygen supply during ischaemia decreases mitochondrial ATP production and increases the generation of free radicals (O2-., OH-.). By diminishing the bioavailability of free radicals, trimetazidine lessens all their toxic effects: trimetazidine acts on the inactivation of enzymatic membrane proteins (which induces ATP over-reduction, creatine phosphokinase and lactate release outside the cell and electrolyte shifts); trimetazidine corrects the elevation of passive membrane permeability (increased by free radical-induced peroxidation of unsaturated membrane lipids); it antagonises free radical-induced stimulations of phospholipase A2 and thromboxane synthetase. In conclusion, trimetazidine restores energy-producing processes in the ischaemic heart cell by lessening the toxic effects of oxygenated free radicals.
与传统抗心绞痛药物相比，曲美他嗪似乎是一种非常特异性的治疗药物，尤其是对缺血细胞。β受体阻滞剂、硝酸盐和钙拮抗剂均作用于真正的缺血区域之外（作用于外周静脉或动脉、冠状血管、全心肌收缩力、窦房结、心内膜-心外膜血流比值等），而曲美他嗪仅对缺血诱导的膜功能丧失及其后果有效。缺血期间组织氧供应的紊乱会减少线粒体ATP的产生并增加自由基（超氧阴离子、羟自由基）的生成。通过降低自由基的生物利用度，曲美他嗪减轻了它们所有的毒性作用：曲美他嗪作用于膜酶蛋白的失活（这会导致ATP过度还原、肌酸磷酸激酶和乳酸释放到细胞外以及电解质移位）；曲美他嗪纠正被动膜通透性的升高（自由基诱导的不饱和膜脂质过氧化作用使其增加）；它拮抗自由基诱导的磷脂酶A2和血栓素合成酶的刺激。总之，曲美他嗪通过减轻氧化自由基的毒性作用来恢复缺血心肌细胞中的能量产生过程。
