New data on well-known drug: focus on meldonium

Abstract

The article reviews the efficacy of meldonium in patients with various diseases, which are based on secondary mitochondrial dysfunction. Mitochondria are complex cellular organelles that control many metabolic processes, including fatty acid oxidation, the Krebs cycle, oxidative phosphorylation in the electron transport chain, and many other processes. Many conditions can lead to secondary mitochondrial dysfunction and affect other diseases. Damage to mitochondria can promote the activation of free radical processes and the initiation of the mechanisms of programmed cell death, mitochondrial dysfunction decrease in the immune response, increase in the activity of the body’s inflammatory response in various infections. Mitochondria appear to be important in COVID-19 pathogenesis because of its role in innate antiviral immunity, as well as inflammation. The article presents data on the effectiveness of using meldonium as a drug that helps to arrest pathological processes in mitochondria. The main mechanism of action of meldonium is based on a decrease in L-carnitine levels and increase of peroxisomes activity in the cytosol Meldonium was designed as a inhibitor of carnitine biosynthesis aimed to prevent accumulation of cytotoxic intermediate products of fatty acid beta- oxidation in ischemic tissues and to block this highly oxygen- consuming process. It is based on the correction of the energy metabolism of the cell. There was a positive trend in the use of meldonium in patients with diseases of the cardiovascular system (chronic ischemic diseases, chronic heart failure, arterial hypertension, etc.), neurological disorders (stroke, cerebrovascular insufficiency, etc.), respiratory diseases. The data on the beneficial effect of meldonium on the immune response in patients with coronavirus, bronchial asthma, chronic obstructive pulmonary disease, during vaccination with anti-influenza serum are presented. A decrease in asthenia was noted against the background of the use of meldonium in patients who had undergone coronavirus infection.

Unlocking the Potential of Meldonium: From Performance Enhancement to Therapeutic Insights

“…Meldonium exerts its mechanism of action primarily through inhibiting γ-butyrobetaine hydroxylase (BBOX), a 2-oxoglutarate (2OG) oxygenase involved in the final step of carnitine biosynthesis [15]. By inhibiting this enzyme, meldonium decreases L-carnitine levels, leading to an increase in peroxisome activity in the cytosol [16]. This inhibition of carnitine biosynthesis aims to prevent the accumulation of cytotoxic intermediate products of fatty acid beta-oxidation in ischemic tissues, thereby reducing tissue damage [16].…”

“…By inhibiting this enzyme, meldonium decreases L-carnitine levels, leading to an increase in peroxisome activity in the cytosol [16]. This inhibition of carnitine biosynthesis aims to prevent the accumulation of cytotoxic intermediate products of fatty acid beta-oxidation in ischemic tissues, thereby reducing tissue damage [16]. Moreover, meldonium has been shown to compete with organic cation transporter 2 (OCTN2), leading to the elimination of carnitine through urine and a subsequent decrease in tissue carnitine content [17].…”