title: Antinociceptive effect of novel trihalomethyl-substituted pyrazoline methyl esters in formalin and hot-plate tests in mice.
abstract: The aim of the present study was to evaluate the antinociceptive potential of four novel pyrazoline methyl ester compounds on chemical and thermal models of pain in mice. The following 5-trihalomethylated-4,5-dihydro-1H-pyrazole methyl ester compounds were tested: 3-methyl-5-trifluoromethyl-(MPF3), 4-methyl-5-trifluoromethyl-(MPF4), 3-methyl-5-trichloromethyl-(MPCl3) and 4-methyl-5-trichloromethyl-(MPCl4). MPF3, MPF4, MPCl3 and MPCl4 (0.03-1.0 mmol/kg) given intraperitoneally decreased neurogenic and inflammatory phases of nociception in the formalin test. Moreover, MPF3, MPF4, MPCl3, MPCl4 (0.1-1.0 mmol/kg) and dipyrone (1.5 mmol/kg) also produced a dose-dependent antinociceptive effect in the hot-plate test. However, MPF3, MPF4, MPCl3 and MPCl4 did not impair motor coordination in the rotarod test or spontaneous locomotion in the open field test. The antinociceptive effect of MPF4 (1.0 mmol/kg, i.p.) was reversed by the opioid receptor antagonist naloxone (2 mg/kg, i.p.), but not by the alpha(2)-adrenergic receptor antagonist yohimbine (0.15 mg/kg, i.p.) or by p-chlorophenylalanine ethyl ester (PCPA, 300 mg/kg, i.p.) treatment. In contrast to morphine (5 mg/kg, i.p.), MPF4 given daily for up to 8 days did not generate a tolerance to its antinociceptive effect. However, similar to morphine (11 mg/kg, i.p.), MPF4 reduced gastrointestinal transit in mice. Taken together these results demonstrate that these novel pyrazoline methyl esters tested may be promising prototypes of additional mild analgesics.
authors.affiliation: Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Química, Centro de Ciências Naturais e Exatas, Brazil.
authors.forename: Julie
authors.initials: J
authors.lastname: Milano
authors.forename: Sara M
authors.initials: SM
authors.lastname: Oliveira
authors.forename: Mateus F
authors.initials: MF
authors.lastname: Rossato
authors.forename: Patricia D
authors.initials: PD
authors.lastname: Sauzem
authors.forename: Pablo
authors.initials: P
authors.lastname: Machado
authors.forename: Paulo
authors.initials: P
authors.lastname: Beck
authors.forename: Nilo
authors.initials: N
authors.lastname: Zanatta
authors.forename: Marcos A P
authors.initials: MA
authors.lastname: Martins
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Mello
authors.forename: Maribel A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Helio G
authors.initials: HG
authors.lastname: Bonacorso
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005772:Gastrointestinal Transit / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000379:methods*; D011720:Pyrazoles / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D011720:Pyrazoles