Antinociceptive, anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H-Pyrazole-3-carbohydrazide, a new heterocyclic pyrazole derivative

作者：Malvar David do Carmo^*; Ferreira Raquel Teixeira; de Castro Raphael Andrade; de Castro Ligia Lins; Carreira Freitas Antonio Carlos; Costa Elson Alves; Florentino Iziara Ferreira; Martins Mafra Joao Carlos; Petto de Souza Gloria Emilia; Vanderlinde Frederico Argollo

来源：Life Sciences, 2014, 95(2): 81-88.

DOI：10.1016/j.lfs.2013.12.005

• 1.5-Diphenyl-1H-Pyrazole-3-carbohydrazide
• Anti-inflammatory activity
• Antinociceptive activity
• Antipyretic activity
• Cyclooxygenase
• PGE(2)
• TNF-alpha

Aims: Heterocyclic pyrazole derivative has been described for the treatment of pain and inflammatory diseases. This study evaluated the in vivo, antinociceptive, anti-inflammatory and antipyretic effects of 1.5-dipheny1-1HPyrazole-3-carbohydrazide (1.5-DHP) and the in vivo or in vitro mechanism of action.
Main methods: Acetic acid-induced writhing, hot-plate and formalin-induced nociception tests were used to evaluate the antinociceptive effect, while the rota-rod test was used to assess the motor activity. Croton oil-induced ear edema and carrageenan-induced peritonitis tests were used to investigate the anti-inflammatory effect of 1.5-DHP. The antipyretic effect was assessed using the LPS-induced fever model. The mechanism of action was evaluated by PGE(2) and TNF-alpha measurement and cyclooxygenase inhibition assay.
Key findings: Oral administration (p.o.) of 1.5-DHP (1, 3, 10 mg/kg) caused a dose-related inhibition of the acetic acid-induced writhing, however the highest dose was not effective on the hot-plate and rota-rod. In the formalin-induced nociception, 1.5-DHP (10 mg/kg, p.o.) inhibited only the late phase of nociception. This same dose of 1.5-DHP also reduced the croton oil-induced ear edema. 1.5-DHP (3, 10, 30 mg/kg, p.o.) produced a dose-related reduction of leukocyte migration on the carrageenan-induced peritonitis. 1.5-DHP (60 mg/kg, p.o.) reduced the fever and the increase of PGE(2) concentration in the cerebrospinal fluid induced by LPS. 1.5-DHP inhibited both COXs in vitro. Finally, 1.5-DHP (10 mg/kg, p.o.) reduced the TNF-alpha concentration in peritoneal exudates after carrageenan injection.
Significance: These results indicate that 1.5-DHP produces anti-inflammatory, antinociceptive and antipyretic effects by PGE(2) synthesis reduction through COX-1/COX-2 inhibition and by TNF-alpha synthesis/release inhibition.

• 出版日期2014-1-30