Mildronate (3- (2,2,2-trimethylhydrazine) propionate) is a drug that reversibly blocks gamma-butyrobetaine hydroxylase, which catalyzes the conversion of gamma-butyrobetaine to carnitine and thereby significantly inhibits the intake of carnitine, which is responsible for the transfer of fatty acids through the cellular membrane of muscle tissue.
This effect of Mildronate followed by a decrease in the carnitine-dependent oxidation of free fatty acids (FFA) and, consequently, leads to activation of glucose oxidation, which is preferable in the conditions of ischemia. An important feature of Mildronate mechanism of action, which distinguishes it from other drugs that affect the metabolism of the myocardium, is the lack of accumulation of under-oxidized fatty acids inside the mitochondria, and lack of increase in the production of nitric oxide in tissues. Mildronate has been extensively studied in various forms of ischemic heart disease (angina pectoris, myocardial infarction), and as a preparation of preoperative preparation (aorto-coronary shunt) under chronic heart failure.
In the conducted studies, it was shown that mildronate improves the transferability of physical exertion and the quality of life of patients, positively affects the functional parameters of the heart and systolic volume, without causing significant side effects. Meldonium is the drug of choice in the initial stage of the cardiac insufficiency and can be included in various therapeutic regimens.
There is a sufficient number of publications on the use of mildronate in neurology and psychiatry. The authors pay special attention to the pathogenesis of acute neurological pathology: the formation of an energy deficit in the brain tissue during the first hours of development of cerebral ischemia, the destruction of calcium metabolism, and the development of lactate acidosis, which decrease towards the end of the first day.
Further, after 12-36 hours, oxidative stress and inflammation develops, and in 2-3 days – apoptosis, which persists for a long period of time and contributes to the development of encephalopathy. Modern treatment tactics consist of two components: initial restoration of blood flow and the protection of the brain tissue from ischemic damage neuroprotection (cytoprotection, metabolic protection of the brain).
The goal of neuroprotective actions is to delay and eliminate the energy deficit resulting from the restructuring of cell metabolism from the aerobic pathway of glucose oxidation to anaerobic. It was also found that a 6-week treatment course with mildronate in a daily dose of 1000 mg affects cognitive functions and electrophysiological characteristics of the brain.
Mildronate® is used since 1988-1991 in sports medicine and firmly established itself as an effective tool in a complex of recreative therapy, especially in the treatment of chronic physical stress syndrome.
From 1989 to the present, this drug is successfully used in cardiologic practice not only in the complex of restorative treatment but also in acute and subacute forms of the course of ischemic heart disease (IHD), in particular, with acute myocardial infarction.
Thus, the analytical review of the literature on the use of mildronate in various fields of clinical medicine allows us to conclude that the drug is effective and safe in patients with cardiological, neurological profiles. Meldonium can be used in patients with decreased mental and physical performance, myocardial infarction, chest pain, chronic heart failure, retinopathy, and alcohol withdrawal syndrome.