Middronate (also known as THP, MET-88 and mildronate) is a new kind of heart protective drug.
Mitochondrion is the site of action of mitrozide, which can improve myocardial energy metabolism at the cellular level. In view of the obvious difference between these drugs and other anti myocardial ischemia drugs, they are also called cellular anti ischemia drugs.
As a structural analogue of carnitine, midroxide can competitively inhibit butyrate betaine hydroxylase, thereby inhibiting carnitine biosynthesis and directly inhibiting carnitine dependent fatty acid transport in mitochondria. Inhibition of carnitine biosynthesis can reduce the concentration of intracellular free carnitine and prevent accumulation of acyl carnitine induced by isoproterenol. Therefore, this drug has obvious protective effect on myocardium, and has no obvious effect on hemodynamic parameters, and has no obvious change in cardiac blood supply and oxygen consumption.
Membrane protection: myocardial ischemia causes tension reaction of myocardial cells, increases the decomposition of fatty acids in mitochondria, accumulates metabolites of fatty acids in cells, destroys cell membrane devices, and increases intracellular Ca +. The membrane stabilization effect of mirtazidine can protect the calcium uptake of sarcoplasmic reticulum Ca2 + - ATPase (SERCA2), improve the loss of SERCA2 and hexokinase I caused by myocardial infarction, so as to reduce the tissue damage caused by myocardial ischemia and alleviate the hemodynamic dysfunction.
Energy optimization: medroxide can reduce the accumulation of long-chain acyl carnitine, thus inhibiting carnitine dependent fatty acid oxidation, transforming the energy metabolism of hypoxic myocardium from fatty acid oxidation to more favorable glucose oxidation, that is, promoting anaerobic oxidation of glycolysis pathway. Therefore, this product has anti hypoxia effect and cardiac protective activity. In addition, medroxide can inhibit carnitine acetyltransferase, so it can improve the utilization of acetyl CoA by various metabolic pathways in mitochondria, prevent the decrease of ATP and ADP concentration, and prevent the accumulation of AMP and the decrease of energy charge caused by isoproterenol, thus playing a protective role in myocardium.
Effects on energy metabolizing enzymes: mildrohydrazide can also prevent isoproterenol induced enhancement of blood lactate dehydrogenase (myocardial specific isoenzyme) liver alloactivity, and prevent the increase of creatine phosphokinase activity.
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