Mildronate dihydrate is an inhibitor of biosynthesis of L-carnitine by gamma-butyrobetaine (GBB) hydroxylase and as a competitive inhibitor of renal carnitine reabsorption.

OCTN2 (human):21 μM (EC50), BBOX (human recombinant):34-62 μM (IC50)

Mildronate (40 μM) inhibits the reaction of γ-butyrobetaine hydroxylase with γ-butyrobetaine with Km and Vmax of 36.8 μM and 0.08 nmol/min/mg protein, respectively. [1]

Mildronate 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. Mildronate 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 Mildronate 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] Mildronate (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. Mildronate long-term treatment statistically significantly decreases fed state blood glucose from 6 to 5 mM. [2] Mildronate reduces the azidothymidine-induced alterations in mouse brain tissue. Mildronate (50 mg/kg) normalizes the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and iNOS expression. Mildronate also normalizes the changes in cytochromec oxidase (COX) expression, reduces the expression of glial fibrillary acidic protein (GFAP) and cellular infiltration. [3]