title: Antinociceptive, anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H-Pyrazole-3-carbohydrazide, a new heterocyclic pyrazole derivative.
abstract: OBJECTIVE
  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-diphenyl-1H-Pyrazole-3-carbohydrazide (1.5-DHP) and the in vivo or in vitro mechanism of action.
  
  
  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 PGE2 and TNF-α measurement and cyclooxygenase inhibition assay.
  
  
  RESULTS
  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 (10mg/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 PGE2 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-α concentration in peritoneal exudates after carrageenan injection.
  
  
  CONCLUSIONS
  These results indicate that 1.5-DHP produces anti-inflammatory, antinociceptive and antipyretic effects by PGE2 synthesis reduction through COX-1/COX-2 inhibition and by TNF-α synthesis/release inhibition.
authors.affiliation: Universidade Federal Rural do Rio de Janeiro, Instituto de Biologia, Departamento de Ciências Fisiológicas, Seropédica, RJ, Brazil; Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Departamento de Física e Química, Ribeirão Preto, SP, Brazil. Electronic address: dcmalvar@gmail.com.
authors.forename: David do Carmo
authors.initials: Ddo C
authors.lastname: Malvar
authors.affiliation: Universidade Federal Rural do Rio de Janeiro, Instituto de Biologia, Departamento de Ciências Fisiológicas, Seropédica, RJ, Brazil.
authors.forename: Raquel Teixeira
authors.initials: RT
authors.lastname: Ferreira
authors.affiliation: Universidade Federal Rural do Rio de Janeiro, Instituto de Biologia, Departamento de Ciências Fisiológicas, Seropédica, RJ, Brazil.
authors.forename: Raphael Andrade
authors.initials: RA
authors.lastname: de Castro
authors.affiliation: Universidade Federal Rural do Rio de Janeiro, Instituto de Biologia, Departamento de Ciências Fisiológicas, Seropédica, RJ, Brazil.
authors.forename: Ligia Lins
authors.initials: LL
authors.lastname: de Castro
authors.affiliation: Universidade Federal do Rio de Janeiro, Núcleo de Pesquisas de Produtos Naturais, Cidade Universitária, Rio de Janeiro, RJ, Brazil.
authors.forename: Antonio Carlos Carreira
authors.initials: AC
authors.lastname: Freitas
authors.affiliation: Universidade Federal de Goiás, Instituto de Ciências Biológicas, Departamento de Ciências Fisiológicas, Goiânia, GO, Brazil.
authors.forename: Elson Alves
authors.initials: EA
authors.lastname: Costa
authors.affiliation: Universidade Federal de Goiás, Instituto de Ciências Biológicas, Departamento de Ciências Fisiológicas, Goiânia, GO, Brazil.
authors.forename: Iziara Ferreira
authors.initials: IF
authors.lastname: Florentino
authors.affiliation: Universidade Federal do Rio de Janeiro, Núcleo de Pesquisas de Produtos Naturais, Cidade Universitária, Rio de Janeiro, RJ, Brazil.
authors.forename: João Carlos Martins
authors.initials: JC
authors.lastname: Mafra
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Departamento de Física e Química, Ribeirão Preto, SP, Brazil.
authors.forename: Glória Emília Petto
authors.initials: GE
authors.lastname: de Souza
authors.affiliation: Universidade Federal Rural do Rio de Janeiro, Instituto de Biologia, Departamento de Ciências Fisiológicas, Seropédica, RJ, Brazil.
authors.forename: Frederico Argollo
authors.initials: FA
authors.lastname: Vanderlinde
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D058633:Antipyretics / Q000737:chemistry / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D015232:Dinoprostone / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects*; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C587182:1,5-diphenyl-1H-pyrazole-3-carbohydrazide; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D058633:Antipyretics; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D011720:Pyrazoles; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone
keywords: 1.5-Diphenyl-1H-Pyrazole-3-carbohydrazide; Anti-inflammatory activity; Antinociceptive activity; Antipyretic activity; Cyclooxygenase; PGE(2); TNF-α