Mildronate and its Neuroregulatory Mechanisms: Targeting the Mitochondria, Neuroinflammation, and Protein Expression

Abstract

This review for the first time summarizes the data obtained in the neuropharmacological studies of mildronate, a drug previously known as a cardioprotective agent. In different animal models of neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By the use of immunohistochemical methods and Western blot analysis, as well as some selected behavioral tests, the new mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on the expression of nerve cell proteins, which are involved in cell survival, functioning, and inflammation processes. Particular attention is paid to the capability of mildronate to stimulate learning and memory and to the expression of neuronal proteins involved in synaptic plasticity and adult neurogenesis. These properties can be useful in neurological practice to protect and treat neurological disorders, particularly those associated with neurodegeneration and a decline in cognitive functions.

Mildronate (Meldonium) in professional sports – monitoring doping control urine samples using hydrophilic interaction liquid chromatography – high resolution/high accuracy mass spectrometry

“…Further studies demonstrated an increase in endurance performance of athletes, improved rehabilitation after exercise, protection against stress, and enhanced activations of central nervous system (CNS) functions . Moreover, Mildronate shows mood‐improving effects as well as an increased learning and memory performance, which are properties athletes may also benefit from . In dubious online shops, the performance‐enhancing effects of Mildronate are advertised overtly .…”

Story behind meldonium–from pharmacology to performance enhancement: a narrative review

“…One concept of the neurological actions of meldonium is that due to its structural similarity to L-carnitine, it could act as a carnitine-mimicking substance (‘false carnitine’28). High concentrations of meldonium should lead to a negative feedback, with the consequence of a compensatory decrease in intracellular L-carnitine.…”

“…High concentrations of meldonium should lead to a negative feedback, with the consequence of a compensatory decrease in intracellular L-carnitine. Therefore, meldonium was suggested to fulfil the criteria as a replacement medication for L-carnitine 28. In different animal models of neurotoxicity and neurodegenerative diseases, meldonium was shown to exhibit beneficial effects in the regulation of neuroinflammation, neuroregeneration and apoptosis, with its main actions on the regulation of mitochondrial processes and the expression of nerve-cell proteins 28–32.…”

“…In addition, memory-enhancing effects31 and positive effects on stress-induced memory impairment35 were reported. Despite the fact that clinical trials are at present missing, it is much speculated that in the future meldonium could be applied in neurological disorders (eg, Parkinson’s disease), diabetic neuropathies and stroke and also in neurological conditions with cognitive impairment (eg, neurodegenerative diseases and schizophrenia) 28. In summary, the scientific level of evidence that meldonium is of clinical importance in neurological diseases is at present low.…”

Препарат Мельдоний У пациентов С ишемическим Инсультом В раннем Восстановительном Периоде

“…В ряде клинических наблюдений была показана высокая эффективность мельдония при острой церебральной ишемии, заключавшаяся в зна-чимом регрессе основных клинико-неврологических симптомов, улучшении когнитивных функций, норма-лизации биоэлектрической активности головного моз-га и показателей гемодинамики [4,7,14,20]. При этом эффективность данного препарата, по мнению исследо-вателей, напрямую связана с его воздействием на меха-низмы энергокоррекции [3,15,16]. Кроме того, за счет индуцирования эндотелиальной NO-синтазы, стиму-лирующей синтез NO, а также вазодилатации, мельдо-ний оказывает позитивное действие на гемодинамику ишемизированных зон головного мозга [8,9,12,18,20].…”