Mildronate: mechanism of action, clinical applications and side effect

General Description

Mildronate is a medication that has been extensively studied for its use in treating cardiovascular disorders. Its mechanism of action involves inhibiting carnitine biosynthesis, decreasing carnitine transport, and promoting glucose oxidation, which helps maintain cellular function during ischemic conditions and improves cellular survival. Clinical studies have shown that mildronate is an effective treatment for chronic heart failure and coronary insufficiency, with comparable efficacy to digoxin. Mildronate also optimizes oxygen consumption and can be used during acute periods of myocardial infarction. However, potential side effects such as tachycardia, abrupt changes in blood pressure, allergic reactions, digestive symptoms, and psychomotor overexcitation should be closely monitored. Overall, mildronate has proven to be a useful medication in treating cardiovascular disorders, but its use should be carefully considered under the guidance of a healthcare professional.

Figure 1. Capsules of mildronate

Mechanism of action

The mechanism of action of mildronate involves several pathways. Firstly, it lowers the intracellular concentration of free carnitine, which inhibits the oxidation of fatty acids and promotes glycolysis during ischemia. Mildronate inhibits the biosynthesis of carnitine by acting as a competitive inhibitor of -butyrobetaine (GBB) hydroxylase, an enzyme involved in the production of carnitine. Furthermore, mildronate decreases the pool of carnitine by inhibiting its reabsorption in the kidneys, leading to its direct elimination from the body. This inhibition of renal carnitine transport regulates the carnitine content in the body. Mildronate also affects the transport of carnitine into muscle cells by a noncompetitive mechanism. In addition to its effects on carnitine metabolism, mildronate also influences glucose oxidation. It increases the steady state of glucose oxidation in the heart, decreases lactate concentration, and increases ATP levels after coronary artery occlusion. Mildronate also enhances the protein content of enzymes involved in glucose metabolism and activates the reuptake of calcium by the sarcoplasmic reticulum, reducing tissue damage caused by ischemia. Overall, mildronate's mechanism of action involves inhibiting carnitine biosynthesis, decreasing carnitine transport, and promoting glucose oxidation. These effects contribute to the maintenance of cellular functions during ischemic conditions and improve cellular survival. ¹

Clinical applications

Mildronate is a drug that has been clinically investigated in Russia, Ukraine, and Latvia over the past decade for treating cardiovascular disorders. The studies conducted revealed that mildronate is an effective treatment for chronic heart failure and coronary insufficiency. According to New York Heart Association classification, the cardioprotective effect of mildronate was proven in these conditions. The clinical effect of mildronate was also comparable to digoxin in treating ischemic heart disease and chronic heart failure. Moreover, Mildronate optimizes oxygen consumption and can be used during acute periods of myocardial infarction. Positive effects of mildronate were also observed in heart functioning, physical activity, and life quality for heart-failure patients. The studies suggested that the regulatory effect of mildronate on carnitine content is responsible for its cardioprotective mechanism. This regulatory effect switches the energy metabolism from fatty acid oxidation to the more favorable glucose oxidation, thus reducing the development of cardiovascular disorders. In conclusion, biochemical, pharmacological, and clinical evidence supports the use of mildronate to treat cardiovascular disorders and reduce the risk of heart failure and coronary insufficiency. ²

Side effect

Mildronate is a medication commonly used to treat certain cardiovascular conditions. However, it is important to be aware of its potential side effects. Tachycardia, which refers to an abnormally fast heart rate, may occur as a result of taking Mildronate. Another possible side effect is an abrupt change in blood pressure, leading to fluctuations in both high and low levels. Allergic reactions are also possible, characterized by redness, itching, and swelling. Additionally, Mildronate can cause digestive symptoms such as eructations (burping), flatulence, and other signs of dyspepsia. Lastly, some individuals may experience psychomotor overexcitation, leading to increased restlessness and agitation. It is important to consult a healthcare professional for further guidance and to closely monitor any potential adverse reactions while taking Mildronate. ³

Reference

1. Klusa V, Beitnere U, Pupure J, et al. Mildronate and its neuroregulatory mechanisms: targeting the mitochondria, neuroinflammation, and protein expression. Medicina (Kaunas). 2013;49(7):301-309.

2. Dambrova M, Liepinsh E, Kalvinsh I. Mildronate: cardioprotective action through carnitine-lowering effect. Trends Cardiovasc Med. 2002;12(6):275-279.

3. Klusa V, Pupure J, Isajevs S, et al. Protection of azidothymidine-induced cardiopathology in mice by mildronate, a mitochondria-targeted drug. Basic Clin Pharmacol Toxicol. 2006;99(4):323-328.