Abstract
Among N-(4-methoxybenzyl)-4-methyl-2.2-dioxo-1H-2 λ6.1-benzothiazine-3-carboxamide derivates, the compound methoxybenzyl-amide derivative 4-methyl-2.2-dioxo-1H-2λ6.1-benzothiazine-3-carboxylic acid (compound NI-9) with pronounced analgesic and anti-inflammatory activities, which was superior to those of diclofenac and lornoxicam in the model of carrageenan edema. The aim of the study was to investigate the analgesic effect of benzothiazine-3-carboxamide derivative on different models of somatic and neuropathic pain syndromes. The study was performed on 91 male Wistar rats. Compound NI-9 and reference drugs meloxicam, diclofenac and gabapentin were administered intragastrically at doses of 3, 5, 8 and 5 mg/kg, respectively, corresponding to their ED50 in analgesic activity. Acetic spasms in mice, a model of thermal irritation of the tail flick in rats, as well as adjuvant arthritis and diabetic polyneuropathy were selected as models of pain syndromes. The results were processed in the program STATISTICA 10.0 using non-parametric methods. The results showed that methoxybenzyl-amide derivative 4-methyl-2.2-dioxo-1H-2λ6.1-benzothiazine-3-carboxylic acid (compound NI-9) has a pronounced analgesic effect on various models of pain syndromes, both somatic and inflammatory. and of neurogenic origin. The analgesic activity of the compound NI-9 in the model of acetic acid cramps in mice and thermal irritation in rats was 38.09 and 49.75 %, respectively, which was higher than that of meloxicam (36.73 and 45.68 %), and inferior to diclofenac (41.95 and 55.95 %). In the model of the systemic inflammatory process (adjuvant arthritis), the analgesic effect of NI-9 was statistically superior to meloxicam and diclofenac (43.32 % vs. 26.26 and 33.69 %). In a model of neuropathic pain syndrome (diabetic neuropathy), the analgesic effect of methoxybenzyl-amide derivative 4-methyl-2.2-dioxo-1H-2λ6.1-benzothiazine-3-carboxylic acid was greater than meloxicam (18.96 vs. 13.34 %), but this figure was lower than that of gaapentin (20.83 %). Further in-depth study of its pharmacodynamics and toxicity will be the theoretical basis for the development on the basis of this biologically active compound of the original drug with analgesic and anti-inflammatory activities.
Highlights
Pain is a symptom of most diseases, but is a complex psychophysiological phenomenon, which involves the mechanisms of regulation and formation of emotions, motor, humoral and hemodynamic manifestations that form the pain syndrome [6, 11, 13]
The aim of the study was to investigate the analgesic effect of N-4-methoxybenzyl-amides of 4-methyl-2.2-dioxo1H-2λ6.1-benzothiazine-3-carboxylic acid on various models of somatic and neuropathic pain syndromes
The test substance and reference drugs were administered once i/g for 40 minutes to the action of acetic acid in their conditionally effective analgesic dose (ED50), which was determined in previous experiments or borrowed from the literature and was 3, 5 and 8 mg/kg, respectively
Summary
Pain is a symptom of most diseases, but is a complex psychophysiological phenomenon, which involves the mechanisms of regulation and formation of emotions, motor, humoral and hemodynamic manifestations that form the pain syndrome [6, 11, 13]. According to the International Association of Pain Study (IAPS), "Pain is an unpleasant sensory and emotional experience that is associated with existing or possible tissue damage or as described in terms of such damage" [16]. Chronic pain is the greatest threat to health and quality of life. It has no protective function and has no biological expediency.
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