Effect of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles on chronic inflammatory pain model in rats.
Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used for treatment of arthritis. However, their long-term use has been associated with considerable morbidity, limiting their application. Thus, there remains a need to develop new drugs for the effective and safe relief of chronic inflammatory pain. In this context, the present study was designed to evaluate the antinociceptive and antiedematogenic effects of the 5-trifluoromethyl-4,5-dihydro-1H-pyrazole derivatives EPFCA3 and MPFCA4 after acute (1-1000 micromol/kg) and chronic (100 micromol/kg for 15 days) administration in rats submitted to a model of adjuvant-induced arthritis. We also analyzed some biochemical indicators of toxicity (alanine aminotransferase, aspartate aminotransferase, urea and creatinine levels) after prolonged administration of these compounds. We found that acute and chronic subcutaneuous administration of EPFCA3 and MPFCA4 produces an antinociceptive, but not antiedematogenic, effect on the arthritis animal model induced by complete Freund's adjuvant (CFA). No signs of toxicity were observed in the animals chronically treated with EPFCA3 or MPFCA4. Dipyrone (1-1000 micromol/kg) was used as the positive control and its effect was similar to that of the novel pyrazoles. The activity of tissue myeloperoxidase, the tissue TNF-alpha level and the serum haptoglobin level was increased by intraplantar CFA injection. However, chronic administration of EPFCA3, MPFCA4 or dipyrone was not able to alter the relation between these parameters and inflammation. Our results suggest that EPFCA3 and MPFCA4 are good candidates for the development of new drugs for pain treatment.
Sauzem
Patricia D
PD
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Sant'Anna
Gabriela da S
Gda S
Machado
Pablo
P
Duarte
Marta M M F
MM
Ferreira
Juliano
J
Mello
Carlos F
CF
Beck
Paulo
P
Bonacorso
Helio G
HG
Zanatta
Nilo
N
Martins
Marcos A P
MA
Rubin
Maribel A
MA
D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease / Q000188:drug therapy; D003404:Creatinine / Q000097:blood; D004177:Dipyrone / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D006242:Haptoglobins / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010146:Pain / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014508:Urea / Q000097:blood
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D006242:Haptoglobins; D011720:Pyrazoles; D014409:Tumor Necrosis Factor-alpha; D004177:Dipyrone; D014508:Urea; D003404:Creatinine