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Recent studies have demonstrated the antinociceptive, anti-inflammatory, and gastric protective effects of trimetazidine (TMD) on various models in rats. The present study proposes to demonstrate the antinociceptive action in mice, evaluated in conditions of inflammatory pain, together with the determination of the type of pharmacodynamic interaction between trimetazidine and ketoprofen (KETO). In this study we used as experimental model of nociception the abdominal constrictive response (writhing test), induced with Zymosan A in mice, and for the study of the interaction we used as quantitative evaluation method the method of binary combinations in fixed proportions. The experimental results allowed the demonstration of the ED50 for ketoprofen (DE50 = 0,606 ± 0,108 mg/kg) and the demonstration of the synergism for the associated substances. (Zadd = 1.818 ± 0.326mg/kg, Zmix = 0.458 ± 0.101 mg/kg, y = 0.251, Tc = 4.92, Tt = 3.84, P< 0.05). The results demonstrate that for the same level of activity (50%), smaller doses of each substance can be used, compared to the doses of the substances administered alone, which might contribute to a reduction in the number or severity of adverse effects, on the other side, the demonstration of the synergism might contribute to the clarification of the action mechanisms. The experiments presented below were made in agreement with the rules and regulations concerning the work with lab animals. [ABSTRACT FROM AUTHOR]

Recent research in the field of algesiology demonstrated the existence of several types of pain, with complex mediation cascades. This fact prompted the use of compounds from other drug families than classical analgesics for the treatment of pain. The purpose of this paper is to demonstrate the antinociceptive action of sodium valproate in mice. This investigation relies on three nociception models that use chemical, thermal, mechanical (pressure) stimuli, and a model of acute inflammation induced by carrageenan. The investigations were made using male white Swiss mice, weighing 20-30 grams. Valproate administration has been made orally, using geometric progression dose sequences. According to the statistical analysis, we obtained values of ED50 for sodium valproate for each nociception model as follows: ED50 = 21.773 ± 6.786 mg/kg for the nociception model with Zymosan A, ED50 = 11.807 ± 4.035 mg/kg, for the hot plate test, ED50 = 19.247 ± 2.207 mg/kg for the Randall-Sellitto test. The action of the valproate is explained by the inhibition of pro-inflammatory cytokines like TNF-α IL1β, IL6 and prostaglandin mediators like PGE2. The experiments were made according to the European and Romanian legislation that concerns working with lab animals. [ABSTRACT FROM AUTHOR]