Known and new ideas about the mechanism of action and spectrum of effects of Mexidol

Author:
© T.A. VORONINA1, S.A. LITVINOVA1, N.A. GLADYSHEVA1, A.V. SHULYNDIN2

1Federal Research Center for Original and Promising Biomedical and Pharmaceutical
Technologies, Moscow, Russia;
2Volga Region Research Medical University of the Ministry of Health of the Russian Federation, Nizhny Novgorod, Russia

Place of publication:
S.S. Korsakov Journal of Neurology and Psychiatry 2025, Vol. 125, No. 5, pp. 22–33

Abstract: The article
presents the results of a study of the multimodal mechanism of action of the original Russian drug Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), which provides a neuroprotective effect and a broad spectrum 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 functioning of receptors and ion channels. Succinate in Mexidol provides the ability to induce the succinate receptor SUCNR1, improve succinate signaling, stimulate mitochondriogenesis, restore mitochondrial respiration, activate the Krebs cycle, and improve the energy status of the cell, which determines the antihypoxic effect. Mexidol enhances the expression of transcription factors HIF-1α and Nrf2 under hypoxic conditions. It exhibits neuroregenerative activity mediated by increased levels of key regulatory molecules—neurotrophic factors NGF, IGF1, BDNF, and VEGF—in areas of ischemic brain injury. It also positively influences PGC-1α, which coordinates aerobic metabolism and cellular energy stability. These properties distinguish Mexidol from other succinic acid preparations.

Key words: Mexidol, ethylmethylhydroxypyridine succinate, antioxidant, antihypoxant, neuroprotection, mitochondriogenesis
, succinate signaling, neurotrophic factors, transcription factors.

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