Pharmacological effects of meldonium: Biochemical mechanisms and biomarkers of cardiometabolic activity

  • Pharmacol Res. 2016 Nov;113(Pt B):771-780. doi: 10.1016/j.phrs.2016.01.019.
Maija Dambrova  1 ,  Marina Makrecka-Kuka  2 ,  Reinis Vilskersts  3 ,  Elina Makarova  2 ,  Janis Kuka  2 ,  Edgars Liepinsh  2
Affiliations
  • 1. Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia; Riga Stradins University, Dzirciema Str. 16, Riga LV-1007, Latvia. Electronic address: [email protected].
  • 2. Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
  • 3. Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia; Riga Stradins University, Dzirciema Str. 16, Riga LV-1007, Latvia.
PMID: 26850121 DOI: 10.1016/j.phrs.2016.01.019
Abstract

Meldonium (mildronate; 3-(2,2,2-trimethylhydrazinium)propionate; THP; MET-88) is a clinically used cardioprotective drug, which mechanism of action is based on the regulation of energy metabolism pathways through l-carnitine lowering effect. l-Carnitine biosynthesis enzyme γ-butyrobetaine hydroxylase and carnitine/organic cation transporter type 2 (OCTN2) are the main known drug targets of meldonium, and through inhibition of these activities meldonium induces adaptive changes in the cellular energy homeostasis. Since l-carnitine is involved in the metabolism of fatty acids, the decline in its levels stimulates glucose metabolism and decreases concentrations of l-carnitine related metabolites, such as long-chain acylcarnitines and trimethylamine-N-oxide. Here, we briefly reviewed the pharmacological effects and mechanisms of meldonium in treatment of heart failure, myocardial infarction, arrhythmia, atherosclerosis and diabetes.

Keywords
Cardioprotective; Long-chain acylcarnitines; Meldonium; Trimethylamine-N-oxide; l-Carnitine.
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