Antinociceptive effect of a novel tosylpyrazole compound in mice.
Pain is the most common complaint in the medical field and the identification of compounds that can effectively treat painful states without induction of side-effects remains a major challenge in biomedical research. The aim of the present study was to investigate the antinociceptive effect of a novel compound, 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole (compound A) in several models of pain in mice and compare with those produced by the known trifluoromethyl-containing pyrazole compound celecoxib. Compound A or celecoxib were administrated by oral (78-780 micromol/kg), intrathecal (9-22.5 nmol/site) or intracerebroventricular (9-22.5 nmol/site) routes. Oral administration of either compound A or celecoxib abolished the mechanical allodynia, but not the oedema caused by intraplantar injection of carrageenan. Similarly, compound A reduced the overt nociception, but not the oedema, produced by bradykinin or capsaicin. However, compound A (500 micromol/kg, orally) did not alter nociception nor oedema caused by intraplantar injection of prostaglandin E(2 )or glutamate, whereas celecoxib reduced only the nociception induced by the former. Moreover, oral and intrathecal administration of compound A or celecoxib also reduced the nociception induced by acetic acid. However, only celecoxib reduced the acetic acid-induced nociception when it was injected by the intracerebroventricular route. Finally, neither compound A nor celecoxib was able to produce antinociceptive effect in the tail-flick test or to alter the motor performance and the body temperature. Besides, compound A or celecoxib did not induce gastric lesion. Thus, compound A seems to be an interesting prototype for the development of novel analgesic drugs.
Oliveira
Sara M
SM
Department of Chemistry, Laboratory of Neurotoxicity and Psychopharmacology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.
Gewehr
Camila
C
Dalmolin
Gerusa D
GD
Cechinel
Cleber A
CA
Wentz
Alexandre
A
Lourega
Rogério V
RV
Sehnem
Ronan C
RC
Zanatta
Nilo
N
Martins
Marcos A P
MA
Rubin
Maribel A
MA
Bonacorso
Helio G
HG
Ferreira
Juliano
J
D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D005260:Female; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
C539486:3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D014105:Tosyl Compounds