title: Pharmacological effects of meldonium: Biochemical mechanisms and biomarkers of cardiometabolic activity.
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.
authors: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia; Riga Stradins University, Dzirciema Str. 16, Riga LV-1007, Latvia. Electronic address: maija.dambrova@farm.osi.lv.
authors: Maija
authors: M
authors: Dambrova
authors: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors: Marina
authors: M
authors: Makrecka-Kuka
authors: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia; Riga Stradins University, Dzirciema Str. 16, Riga LV-1007, Latvia.
authors: Reinis
authors: R
authors: Vilskersts
authors: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors: Elina
authors: E
authors: Makarova
authors: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors: Janis
authors: J
authors: Kuka
authors: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors: Edgars
authors: E
authors: Liepinsh
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008763:Methylhydrazines / Q000494:pharmacology* / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate
keywords: Cardioprotective; Long-chain acylcarnitines; Meldonium; Trimethylamine-N-oxide; l-Carnitine