Anti-nociceptive and anti-inflammatory activities of 4-[(1-phenyl-1H-pyrazol-4-yl) methyl] 1-piperazine carboxylic acid ethyl ester: A new piperazine derivative

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2015-10, Vol.137, p.86-92
• Main Authors: Silva, Daiany P.B., Florentino, Iziara F., Oliveira, Lanussy P., Lino, Roberta C., Galdino, Pablinny M., Menegatti, Ricardo, Costa, Elson A.
• Format: Article
• Language: English
• Subjects: Analgesics - chemistry; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Anti-nociception; Dose-Response Relationship, Drug; Edema - drug therapy; Edema - metabolism; Inflammation; LQFM-008; Male; Mice; Pain Measurement - drug effects; Pain Measurement - methods; Piperazine derivative; Piperazines - chemistry; Piperazines - pharmacology; Piperazines - therapeutic use; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Receptor, Serotonin, 5-HT1A - metabolism
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2015.08.008

Piperazine compounds possess anti-infective, anti-carcinogenic, anxiolytic, hypotensive, anti-hypertensive and vasorelaxant properties and are attractive candidates for the development of new analgesic and anti-inflammatory drugs. This study investigates the anti-nociceptive and anti-inflammatory effects of piperazine derivative 4-[(1-phenyl-1H-pyrazol-4-yl) methyl]1-piperazine carboxylic acid ethyl ester (LQFM-008) and the involvement of the serotonergic pathway. In the formalin test, treatments with LQFM-008 (15 and 30mg/kg p.o.) reduced the licking time in both neurogenic and inflammatory phases of this test. In the tail flick and hot plate tests, LQFM008 treatment (15 and 30mg/kg p.o.) increased latency to thermal stimulus, suggesting the involvement of central mechanisms in the anti-nociceptive effect of LQFM-008. In the carrageenan-induced paw edema test, LQFM-008 (p.o.) at the doses of 15 and 30mg/kg reduced the edema at all tested time points, while the dose of 7.5mg/kg reduced the edema only for the first hour. LQFM-008 (30mg/kg p.o.) reduced both cell migration and protein exudation in the carrageenan-induced pleurisy test. Furthermore, pre-treatment with NAN-190 (0.6mg/kgi.p.) and PCPA (100mg/kgi.p.) antagonized the anti-nociceptive effect of LQFM-008 in both phases of the formalin test. Our data suggest that LQFM-008 possesses anti-inflammatory and anti-nociceptive effects mediated through the serotonergic pathway. •Chemical modifications of compounds as strategies for the development of new drugs•New piperazine derivative (LQFM-008) produces analgesic and anti-inflammatory effect.•Serotonergic involvement in the analgesic effect of LQFM-008