SUMMARY
THE EXPERIMENTAL STUDY OF THE ANALGESIC AND ANTIPYRETIC ACTIVITY OF THE NEW MALONIC ACID DERIVATIVES -MALDENN. ?. VakhninaNationalUniversityofPharmacy, Kharkiv Introduction. The article is devoted to the study of analgesic and antipyretic activity of a new compound of di-(2,4-dimethyl) malonic acid anilide under the code name "Maldian". Investigation methods. The studies of analgesic activity of maldian were conducted on the model of "acetic acid writhing" and formalin pain response. The threshold of pain sensitivity (PBC) was determined by the "tail-flick" method. The antipyretic activity was studied in terms of milk fever. As reference drugs used diclofenac sodium 8 mg/kg, metamizole sodium 50 mg/kg, acetylsalicylic acid 50 mg/kg. Results and discussion. The injection of Maldian probably reduced rats pain response that was imprinted with a decrease in the number of "writhing" in 3.1 times (p<0.01) relatively to the control pathology group. The stable tendency towards the maldian excess of the analgesic voltaren action (68,5% and 56.3% respectively) was identified. Analginum as a reference drug statistically significantly 1.8-times (p<0.05) inferior analgesic activity to a new compound. The injection of Maldian at a dose of 7.3 mg/kg has potent analgesic effects on the first and second phases of the formalin pain response. The analgesic activity of di-(2,4-dimethyl) malonic acid anilide was 64.2 percent in the first phase and 97.5 % in the second phase of the experiment. The analgesic effect of the reference drug of analginum became statistically significant different with the control pathology group only during the second phase of formalin pain response. The pharmacological effectiveness of analginum was significantly inferior maldian to antinociceptive activity as in the first and second phases of the pain response. Thus, the tested compound shows a pronounced Central and peripheral antinociceptive effect upon the environment formalin pain response, probably exceeds the analgesic effect of analginum as a reference drug. With the purpose of studying certain aspects of the implementation mechanism of the maldian analgesic action, we have selected the "tail-flick" method termopainful irritation. By analyzing the results of the experiment, we can conclude that the injection of maldian significantly increases PBC experimental animals by 20%, at the same time superiors the effectiveness of the reference drug of voltaren. The last change of PBC was 15%. Summarizing the results of the experiment study of the effect on PBC, it is possible to assume the presence of a Central component of the action in the maldian analgesic effect. The next step of the experiment was to study the possible hypothermic action of maldian in conditions of experimental fever. In animals of the control pathology group it was observed a strong increase in body temperature from the second hour of the experiment, which during the third and fourth hours acquired statistically significant difference relative to baseline (p<0.001). The injection of maldian has had a sustained analgesic effect in experimental fever. It should be noted that the hypothermic effect of the new compounds was identified from the second hour of the experiment, although no statistically significant difference of the gain values to third and fourth. The ability of the tested compound at a dose of 7.3 mg/kg to reduce body temperature in fever conditions, is at the level of the reference drugs of voltaren at a dose of 8 mg/kg and acetylsalicylic acid at a dose of 50 mg/kg. Conclusions. According to the results of the research Maldian can be considered as a promising substance for further pharmacological study and the development of modern domestic drug with analgesic and antipyretic action.References 1. Amelin A.V. Sovremennyye anal'getiki. Stremimsya k effektivnosti i bezopasnosti /A.V.Amelin// Consilium Medicum. - 2015 - ? 02.- S. 34-352. Doklíníchní doslídzhennya líkars'kikh zasobív : metod . rek . / Za red . O. V. Stefanova . - K. : Avítsena , 2001. - 528 s .3. Programma statisticheskogo analiza . Rezhim elektronnogo dostupa www.analystsoft.com/ru4. Rêznikov O. G. Zagal'ní yetichní printsipi yeksperimentív na tvarinakh / O. G. Rêznikov // Yendokrinologíya . - 2003. - T. 8 , ? 1. - S. 142-145 .5. Hunter T.S. Emerging evidence in NSAID pharmacology: important considerations for product selection / T.S. Hunter, C. Robison, P.P. Gerbino //Am J Manag Care.- 2015.-Vol. 21 (7 Suppl).- ?. 139-147. 6. Illés S.T. Low back pain: when and what to do / S.T. Illés // Orv Hetil. -2015.- Vol.156(33). –?. 1315-1320.7. Innaurato G. Analgesia in patients with hepatic impairment / G. Innaurato, V. Piguet, M.L. Simonet // Rev Med Suisse. – 2015.- Vol. 11(480).- ?. 1382-1384.8. Low-dose SoluMatrix diclofenac : a review of safety across two Phase III studies in patients with acute and osteoarthritis pain / A. Gibofsky, R. Altman, S. Daniels et al. // Expert Opin Drug Saf. – 2015.- Vol.14(8).- ?.1327-1339.9. Mkontwana N. Oral analgesia for relieving post-caesarean pain/ N. Mkontwana, N Novikova // Cochrane Database Syst Rev. –2015. – Vol. 29(3) . – ?.450-456. 10. Non-steroidal anti-inflammatory drug administration after coronary artery bypass surgery: utilization persists despite the boxed warning / A. Kulik, K. Bykov, N.K. Choudhry et al. // Pharmacoepidemiol Drug Saf. -2015.- Vol.24(6).- ?.647-653.11. Small molecules with anti-inflammatory properties in clinical development / T. Hanke, D. Merk, D, Steinhilber et al. // Pharmacol Ther. – 2015. – Vol. 25. – ?. 163-168.12. Use of analgesia and sedation in dental implantology in patients with concomitant hypertension / S.I. Sitkin, O.B. Davydova, I.O. Kostin et al. // Stomatologiia. – 2015.- Vol.94(1).- ?. 35-36.