Journal of Pain Research (Dec 2022)
Potent Analgesic Action of 2-acetoxy-5-(2-4 (trifluoromethyl)-phenethylamino)-benzoic Acid (Flusalazine) in Experimental Mice
Abstract
Sung-Soo Kim,1,* Sojung Won,2,* Ha Eun Lee,2 Seung Hyun Ryu,2 Dong Joon Choi,2 Sung Ig Cho,2 Byoung Joo Gwag,2 Hwa-Young Youn,3 Jin Hwan Lee2 1VIP Animal Medical Center KR, Seoul, 02830, Republic of Korea; 2GNT Pharma, Yongin, Gyeonggi, 17096, Republic of Korea; 3Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea*These authors contributed equally to this workCorrespondence: Jin Hwan Lee, GNT Animal Health Business Unit, Yongin, Gyeonggi, 17096, Republic of Korea, Tel +82 10 8878 0456, Fax +82 31 8005 9931, Email [email protected]: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 selective inhibitors are the most widely used drugs to treat pain. Conventional NSAIDs and COX-2 selective inhibitors, however, cause several side effects such as gastric damage, kidney damage, and cardiovascular problems. Our previous study showed that 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid ie, flusalazine (also known as ND-07), which exerts dual actions by serving both as an anti-inflammatory agent and a free radical scavenger, is an effective and safe treatment for severe inflammatory diseases in mice. The goal of the present study was to examine the potential analgesic action and safety of flusalazine in mice models of pain.Methods and Results: Flusalazine showed a significant analgesic effect in an acetic acid-induced abdominal constriction model. Likewise, total paw licking was reduced significantly in neurogenic (early stage) and inflammatory (late stage) pain induced by formalin in flusalazine-treated mice. In the tail immersion test, flusalazine significantly increased tail withdrawal time at 2 h after its administration. Also, the formation of paw edema in the flusalazine-treated group was significantly inhibited in a carrageenan-induced inflammatory pain model. Gastric damage was not induced by flusalazine even up to 1000 mg/kg, while aspirin and indomethacin caused critical gastric bleeding.Conclusion: These findings suggest that flusalazine’s safety profile and analgesic effects have high translational potential for the clinical treatment of patients experiencing pain.Keywords: analgesic effect, aspirin, flusalazine, indomethacin, NSAIDs
