Nefodov O. O., Miasoied Yu. P., Solomenko M. V., Velykorodna-Tanasiichuk O. V., Baklunov V. V., Adehova L. Ia., Gruzd V. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Abstract. For the treatment of nociceptive pain syndromes, including multiple sclerosis, but they can be effective in neuropathic pain (aches, static hyperalgesia, pain in multiple sclerosis), which determines the scientific and practical significance of systemic comparative pharmacological studies of drug mechanisms. Purpose of work: predicting the possibility of combined use of methylprednisolone (as the main means of basic therapy of multiple sclerosis) and meloxicam (as an effective analgesic) under the conditions of the experimental equivalent of multiple sclerosis. Object and methods. Analysis of acid-base properties was performed using the program ACD/pKa DB. Molecular weight, solubility, lipophilicity were determined by additive methods using computer programs. Types of biotargets (receptors, enzymes, transporters) were determined using relevant literature sources. Results. The analysis of functional groups and reactivity of experimental compounds is carried out. Thus, in the molecule of methylprednisolone there are five potential functional groups – three hydroxyl (1-3) and two carbonyl (4,5), which suggests the possibility of its protonation / deprotonation and acid-base properties. There are five potentially reactive groups in the meloxicam molecule, in which the protonation / deprotonation processes can take place in four – vicinal hydroxyl of cyclic structure (group 3) and nitrogen atoms (groups 1, 2 and 5). Next was the analysis of chemical properties and possible interactions. Hydroxyl groups in the molecule of methylprednisolone, as shown from the calculated pKa values, have low acidity, so the possibility of alkylation reactions on them (assuming their participation in nucleophilic substitution reactions as alkoxylating agents) should be considered minimal. However, the participation of methylprednisolone in the nucleophilic addition reactions of the aliphatic substituent of the pregnant ring is possible. In contrast, the relatively mobile proton of hydroxyl in the meloxicam molecule suggests the possibility of participating in both alkylation and acylation reactions. However, methylprednisolone in these conditions, as mentioned above, does not form active charged forms, in the specified pH range shows low solubility in water (polar solvent), so this type of interaction between them should also be considered unlikely. Based on the pKa values of meloxicam and methyl prednisolone, we should not expect protonation reactions on nitrogen atoms, because the considered protolytic forms of methylprednisolone are formed at high pH values. Conclusions. In the presented combination “methylprednisolone-meloxicam” there are no possible interactions both at the physicochemical level (in combination in the dosage form) and at the level of pharmacokinetic stages. The related pharmacological spectrum of methylprednisolone and meloxicam suggests an increased risk of side effects associated with hyperinhibition of prostaglandin biosynthesis and cyclooxygenase biosynthesis (gastrointestinal ulcers), but the synergism of their action allows to reduce the combination of drugs.

experimental allergic encephalomyelitis, multiple sclerosis, analgesia, nonsteroidal anti-inflammatory drugs.

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«Bulletin of problems biology and medicine» Issue 3 (161), 2021 year, 131-136 pages, index UDK 616.832-004.2-092.9:615.212.3

10.29254/2077-4214-2021-3-161-131-136