Meldonium

Meldonium (40 μM) inhibits the reaction of γ-butyrobetaine hydroxylase with γ-butyrobetaine with K_m and V_max of 36.8 μM and 0.08 nmol/min/mg protein, respectively. ^[1]

Meldonium administered orally to rats for 10 days (150 mg/kg) elicits a reduction in myocardial free camitine and long-chain acyl carnitine content by 63.7 and 74.3%, respectively. Meldonium treatment (100 mg/kg, orally) subsequent administration of isoproterenol results in a reduction in free camitine concentration by 48.7% in comparison with the rats receiving isoproterenol. A prior administration of Meldonium effectively protects the myocardium from isoproterenol-induced variations in the content of ATP and myocardial energy charge, as well as preventing a rise in creatine phosphokinase and lactic dehydrogenase activity. ^[1] Meldonium  (200 mg/kg) long-term treatment significantly increases the rate of insulin-stimulated glucose uptake by 35% and the expression of glucose transporter 4 (1.7-fold increase), hexokinase II (2.1-fold increase), insulin receptor proteins (2.5-fold increase) and carnitine palmitoyltransferases IA (2.2-fold increase) in mouse hearts. Meldonium long-term treatment statistically significantly decreases fed state blood glucose from 6 to 5 mM. ^[2] Meldonium reduces the azidothymidine-induced alterations in mouse brain tissue. Meldonium (50 mg/kg) normalizes the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and iNOS expression. Meldonium also normalizes the changes in cytochromec oxidase (COX) expression, reduces the expression of glial fibrillary acidic protein (GFAP) and cellular infiltration. ^[3] Meldonium displays protective effects in experimental model of type 2 diabetes in Goto-Kakizaki rats. Meldonium (200 mg/kg) treatment decreases both the fed- and fasted-state blood glucose. Meldonium strongly inhibits fructosamine accumulation and loss of pain sensitivity (by 75%) and also ameliorates the enhanced contractile responsiveness of Goto-Kakizaki rat aortic rings to phenylephrine. In addition, in Meldonium-treated hearts, the necrosis zone following coronary occlusion is significantly decreased by 30%. ^[4]