Abstract
Non-steroidal anti-inflammatory drugs occupy a leading position in the pharmaceutical market, but their class-specific side effect (ulcerogenic action) significantly limits their widespread use. The N-(4-methoxybenzyl)-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide derivative (compound NI-9) showed a pronounced analgesic effect in various models of pain syndromes. The aim of the study was to determine the effect of a new original derivative of 4-methyl-2.2-dixo-1H-2λ6,1-benzothiazine-3-carboxylic acid on the macroscopic state and biochemical parameters of the gastric mucosa of rats. The study was performed on 51 male Wistar rats. Compound NI-9 and the reference drug meloxicam were administered intragastrically once daily for 28 days at doses of 3 and 5 mg/kg, corresponding to their ED50 analgesic activity. Macroscopic indicators of GM damage, glycosaminoglycan content, phospholipid profile, level of MDA and CGP, as well as nitrates and nitrites and H2S were determined. The results were processed in the program STATISTICA 10.0 using non-parametric methods. The results showed that the carboxamide derivative was safer for the stomach because the ulcer index of compound NI-9 was 1.73 times lower than that of meloxicam. The damaging effect of the compound was more pronounced at the pre-epithelial and epithelial levels of GM protection, while the post-epithelial level (production of vasodilating molecules NO and H2S) was practically unaffected by this derivative, unlike meloxicam, which caused damage at all levels of protection. The obtained data supplement the data on the pharmacodynamics of the 4-methyl-2.2-dixo-1H-2λ6,1-benzothiazine-3-carboxylic acid derivative and determine the expediency of its further studies as a potential non-opioid analgesic.
Highlights
Analysis of the pharmaceutical market of drugs shows that in the arsenal of modern non-narcotic drugs with pronounced analgesic and anti-inflammatory activity an important place belongs to the derivatives of carboxylic acids [9, 16]
Analyzing the macroscopic picture of the gastric mucosa, it should be noted that the compound NI-9 caused less pronounced damage to GM than the comparison drug
Its long-term (28-day) administration caused ulcerative lesions was observed in only 71.4 % of animals against 85.7 % in the group administered meloxicam
Summary
Analysis of the pharmaceutical market of drugs shows that in the arsenal of modern non-narcotic drugs with pronounced analgesic and anti-inflammatory activity an important place belongs to the derivatives of carboxylic acids [9, 16]. According to the chemical structure, drugs of this class can be divided into several groups: first of all derivatives of well-known salicylic acid (aspirin, etc.), derivatives of anthranilic and 2-aminonicotinic acids, which have structural similarity to salicylic acid (mefenamic, flufenamic acid, etc.). Separate mention should be made of derivatives of succinic acid (fenbufen and suxibuzone), hetarylic acid (etodolac and ketorolac), and hetarylacetic acid (indomethacin, sulindac). All of these drugs are the most common group of over-the-counter drugs used by more than 30 million people worldwide, despite the well-known class-specific gastrointestinal side effects (GIs) associated with the free carboxyl group. Carboxylic acids are always of particular interest for the search for promising analgesics [22], and their possible side effects can be eliminated by subsequent chemical transformations into labile non-acidic groups or special conditions of their introduction [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
