Chemoreactome analysis of ethylmethylhydroxypyridine succinate

Ethylmethylhydroxypyridine succinate (EMHPS) is used in the therapy of ischemic stroke. A more complete understanding of the conditions that can affect the clinical efficacy of EMHPS needs the most complete information about its molecular mechanisms of action.

Objective: to comparatively analyze the properties of EMHPS using the newest area of postgenomic pharmacology – chemoreactome simulation. Succinic acid and citicoline were used as the molecules of comparison (control molecules).

Material and methods. Chemoreactome analysis was employed to assess the biological activity of a test molecule (simulation of the affinity profile of the examined molecular structure for various proteome proteins). A new mathematical method based on the combinatorial theory of solvability was devised for chemoinformational analysis.

Results and discussion. Chemoreactome simulation has shown that EMHPS may be an agonist of acetylcholine and GABA receptors, as well as that of cannabinoid receptor type 2. The anti-inflammatory effect of an EMHPS molecule may be due to the inhibition of synthesis of proinflammatory prostaglandins. Its higher safety (a weaker effect on serotonin and opioid receptors and lower interaction with Erg channels and the enzymes monoamine oxidase and cytochrome CYP1A1) distinguish EMHPS from the molecules of comparison (citicolne and succinic acid). The predicted properties of the molecule of EMHPS make a substantial contribution to its neuroprotective effect.

Conclusion. The results of chemoreactome analysis could reveal not only quite unexpected mechanisms of action of EMHPS, but also its mechanisms of synergic action with pyridoxine and magnesium. Owing to a combination of EMHPS with pyridoxine and magnesium, there is an increase in the antioxidant, anticonvulsant, stress- and neuroprotective, nootropic, and anxiolytic effects of EMHPS via activation of pyridoxine-dependent and magnesium-dependent proteins. The combination of EMHPS with pyridoxine and magnesium also contributes to the potentiation of hemodynamic, antiplatelet, antiaggregant, and anticoagulant actions, activates homocysteine neutralization and anti-inflammatory protection, and decreases the risk of proarrhythmic effects.

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