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

• 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

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 30 mg/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 30 mg/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 30 mg/kg reduced the edema at all tested time points, while the dose of 7.5 mg/kg reduced the edema only for the first hour. LQFM-008 (30 mg/kg p.o.) reduced both cell migration and protein exudation in the carrageenan-induced pleurisy test. Furthermore, pre-treatment with NAN-190 (0.6 mg/kg i.p.) and PCPA (100 mg/kg i.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.