The Moldovan Medical Journal (Feb 2017)
Experimental study of new 3-(2-R1 -6-R2 -4-oxyquinoline-3(4H)-yl)alkyl (alkaryl-, aryl) carboxylic acid derivative (PC-66 compound)
Abstract
Background: Screening studies have revealed in new 3-(2-R1-6-R2-4-oxyquinoline-3(4H)-yl)alkyl (alkaryl-, aryl) carboxylic acid derivative (PC-66 compound) expressive analgesic properties without any damaging effects on the stomach. Therefore, in-depth study of the pharmacological properties of PC-66 compound as a pain management agent is considered topical. Objective of the study – to evaluate a pain-killing effect of PC-66 compound compared to ketorolac and diclofenac sodium on various rat pain models. Material and methods: In experiments on 101 Wistar male rats (180-210 g) of somatic model (tail-flick) and neuropathic pain model (ligation of the sciatic nerve), and formalin test (5% formalin solution, 0.1 ml subplantarly) we investigated the antinociceptive activity of the PC-66 compound (1.0 mg/ kg) versus ketorolac (2.4 mg/kg) and diclofenac (4.0 mg/kg) administered intraperitoneally. Results: In the tail-flick model, PC-66 compound presented significant growth of PT at Hour 1 and Hour 2 by 40.6% and 50.6%, respectively. The analgesia effect of the test compound was superior to the one of diclofenac sodium, but inferior to ketorolac at Hour 1 and Hour 2, yet surpassed it by duration of action. In the formalin test model, analgesic effect of compound PC-66 was the most evident in the first (central) phase, and slightly changed the latent period and duration of the second phase of the test, while diclofenac mostly influenced Phase II (inflammatory) of the formalin test. In the model of neuropathic pain, compound PC-66 also demonstrated pronounced pain-killing effect: PT of subject rat limb grew on average by 46.7% in 2 hours following intraperitoneal administration. For this activity, PC-66 was slightly inferior to ketorolac, which caused PT growth by 51.9%. Conclusions: new 3-(2-R1-6-R2-4-oxyquinoline-3(4H)-yl) alkyl (alkaryl-, aryl) carboxylic acid derivative (PC-66 compound) presented distinct analgesic effect both in somatic and neuropathic pain models.
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