The known and new ideas about the mechanism of action and the spectrum of effects of Mexidol
Т. А. Воронина, С. А. Литвинова, Н. А. Гладышева, A.V. Shulyndin
Abstract
The review presents the results of studies concerning the multimodal mechanism of action of the Russian original drug Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), which provides its neuroprotective effect and a wide range of clinical effects. The Mexidol molecule is represented by two related and functionally significant components: 2-ethyl-6-methyl-3-hydroxypyridine and succinate. The presence of 3-hydroxypyridine in the structure of Mexidol is associated with the antioxidant and membranotropic activity of the drug, the ability to reduce glutamate excitotoxicity, and modulate the work of receptors and ion channels. The succinate in Mexidol provides the ability to induce the succinate receptor SUCNR1, improve succinate signaling, stimulate mitochondriogenesis, restore mitochondrial respiration and activate the Krebs cycle, increase the energy status of the cell, which causes the antihypoxic effect of the drug. Mexidol enhances the expression of transcription factors HIF-1α, Nrf2 under hypoxic conditions, has neuroregenerative activity mediated by increased levels of the main regulatory molecules - neurotrophic factors NGF, IGF1, BDNF and VEGF in areas of ischemic brain damage, and also has a positive effect on PGC-1a, which coordinates aerobic metabolism and energy stability of cells. These features distinguish Mexidol from other succinic acid preparations.