TY - JOUR
T1 - Pharmacological effects of meldonium
T2 - Biochemical mechanisms and biomarkers of cardiometabolic activity
AU - Dambrova, Maija
AU - Makrecka-Kuka, Marina
AU - Vilskersts, Reinis
AU - Makarova, Elina
AU - Kuka, Janis
AU - Liepinsh, Edgars
N1 - Funding Information:
This study was supported by the Latvian State Research Programme Biomedicine.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - Cardioprotective
KW - L-Carnitine
KW - Long-chain acylcarnitines
KW - Meldonium
KW - Trimethylamine-N-oxide
UR - http://www.scopus.com/inward/record.url?scp=84971468804&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2016.01.019
DO - 10.1016/j.phrs.2016.01.019
M3 - Review article
C2 - 26850121
AN - SCOPUS:84971468804
SN - 1043-6618
VL - 113
SP - 771
EP - 780
JO - Pharmacological Research
JF - Pharmacological Research
IS - Part B
ER -
