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 (EMHPS), vinpocetine, and nicergoline was conducted using the computational methods of the theory of topological analysis of 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, including: 1) inhibition of the activation of the pro-inflammatory factor NF-κB; 2) decrease in the procoagulant profile; 3) decrease in glutamate excitotoxicity secondary to improved oxygen metabolism. These effects result in conjunction with at least 25 proteins of the human proteome.Conclusion. CDP-choline supports cholinergic neurotransmission and is used in the treatment of vascular pathologies of the brain. The cholinergic effect of CDP-choline is enhanced by the anti-inflammatory, anticoagulant, and neuroprotective action of both the molecule itself and synergistic molecules (in particular, EMHPS).

Keywords

• chronic cerebral ischemia
• data mining
• drug synergism
• cytidyldiphosphocholine
• ethyl-methyl-hydroxypyridine succinate
• betahistine
• vinpocetine
• nicergoline