Mildronate: an Antiischemic Drug with Multiple Indications

Mildronate (3-(2,2,2-trimethylhydrazine)propionate; THP; MET-88; meldonium, quaterine) is an anti-ischemic drug developed in the Latvian Institute of Organic Synthesis. Mildronate was designed as a promising inhibitor of carnitine biosynthesis aimed to prevent accumulation of cytotoxic intermediate products of fatty acid betaoxidation in ischemic tissues and to block this highly oxygenconsuming process. Actually Mildronate is used in several countries in cardiology (treatment of chronic heart ischemic disease, stable angina pectoris, chronic heart failure, functional disorders of heart and vessels, cardiomyopathy, heart infarction), neurology (acute and chronic ischemic brain circulation disorders, decreased work capabilities, physical and emotional overload, recovery period after various diseases), pulmonology (bronchial asthma and obstructive bronchitis), narcology (abstinence syndrome in chronic alcoholism), ophthalmology (hemophthalm and retina haemorrhages of different aetiology, thrombosis of central vein and its branches in retina, diabetic and hypertonic retinopathies). The main mechanism of action of Mildronate is based on carnitine biosynthesis inhibition aimed to prevent accumulation of cytotoxic intermediate products of fatty acid betaoxidation in ischemic tissues and to block this highly oxygen-consuming process. Alternatively the drug acts via stimulation of the nitric oxide production in the vascular endothelium through a modification of the γ-butyrobetaine and γ-butyrobetaine ester pools. The present review will summarize data on the Mildronate on different indications of the drug and its mechanisms of action.