On the mechanisms of the synergistic action of tolperisone, meloxicam and B vitamins in the treatment of peripheral pain syndromes

Abstract

Introduction:The combined use of non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants and group B vitamins is a promising direction for combined pharmacotherapy of peripheral pain syndromes.Purpose:to analyze the molecular mechanisms of the synergism of the muscle relaxant tolperisone, a non-steroidal anti-inflammatory drug meloxicam and vitamins B1, B6and B12as part of complex pharmacotherapy of pain.Materials and methods:differential chemoreactome analysis of NSAID molecules and muscle relaxants, proteomic analysis of the effects of B vitamins.Results:Synergistic interactions are maintained by (1) inhibiting cyclooxygenase-2 and leukotriene A4 hydrolases; (2) inhibition of the effects of IL-1β, TNFα, NF-kB, TLR4, RANKL, matrix metalloproteinases; (3) antioxidant effect (increased expression of superoxide dismutase-1 and glutathione peroxidase). Group B vitamins enhance the effects of tolperisone and meloxicam due to the manifestation of independent anti-inflammatory (neutralization of homocysteine, decreased expression of pro-inflammatory cytokines TNFα, IL-1b and factor NF-kB activity), analgesic (modulation of opioidergic pathways) and neuroprotective effects (support of amino acid expression, metabolism and neuro lipids, ATP synthesis and remyelination).Conclusions:The triple scheme “tolperisone + meloxicam + vitamins B1/ B6/ B12” is characterized by a number of undeniable advantages: (1) lack of dependence, (2) anti-inflammatory effect, (3) neuroprotective and remyelinating effects, (4) elimination of muscle hypertonicity. Such combination therapy can be used in patients of various age groups with comorbid conditions (diabetes mellitus, arterial hypertension, cerebrovascular diseases, gastrointestinal diseases) and does not require an increase in NSAIDs and significantly reduces the risk of side effects.