Chemoreactom analysis of cytidyldiphosphocholine indicates synergistic combinations of neuroprotective agents

Abstract

Objective : to establish the molecular mechanisms of interaction of cytidine-diphosphocholine choline (CDP-choline) with other agents used to treat chronic cerebral ischemia (CCI) to increase the effectiveness of the therapy.. Material and methods. A chemoreactom analysis of CDP-choline, betahistine, ethyl-methyl-hydroxypyridine succinate\xa0 (EMHPS), vinpocetine, and nicergoline was conducted using the\xa0 computational methods of the theory of topological analysis of\xa0 chemographs. Results and discussion . The profiles of the pharmacological action of molecules are described, including the accumulation in tissues, pharmacokinetic and pharmacodynamic parameters, the effect on the metabolome and proteome, the survival of neurons during glutamate stress. The mechanisms of the synergistic action of CDP-choline and EMHPS were discovered,\xa0 including: 1) inhibition of the activation of the pro-inflammatory\xa0 factor NF- κ B; 2) decrease in the procoagulant\xa0 profile; 3) decrease in glutamate excitotoxicity secondary to\xa0 improved oxygen metabolism. These effects result in\xa0 conjunction with at least 25 proteins of the human proteome. Conclusion . CDP-choline supports cholinergic\xa0 neurotransmission and is used in the treatment of vascular\xa0 pathologies of the brain. The cholinergic effect of CDP-choline\xa0 is enhanced by the anti-inflammatory, anticoagulant, and\xa0 neuroprotective action of both the molecule itself and\xa0 synergistic molecules (in particular, EMHPS).