Antinociceptive action of 4-methyl-5-trifluoromethyl-5-hydroxy-4, 5-dihydro-1H-pyrazole methyl ester in models of inflammatory pain in mice.
OBJECTIVE
The aim of the present study was to evaluate the antinociceptive effect of the novel pyrazoline methyl ester: 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF4).


METHODS
The effect of MPF4 was assessed in two models of pain: arthritic pain caused by Complete Freund's Adjuvant (CFA) and postoperative pain caused by surgical incision in mice.


RESULTS
MPF4 given intraperitoneally (1.0 mmol/kg, i.p.) produced marked antinociception in inflammatory allodynia caused by CFA. The antinociceptive effect produced by MPF4 was reversed with the pre-treatment of animals with naloxone or naltrindole. Oral administration of MPF4 (1.0 mmol/kg, p.o), dipyrone (1.0 mmol/kg, p.o.) and morphine (0.026 mmol/kg, p.o.) also produced an anti-allodynic effect. However, none of the compounds evaluated reversed the paw edema produced by CFA. Moreover, MPF4, dipyrone and morphine also produced an anti-allodynic effect in the surgical incisional pain model. The maximal inhibitions obtained with preemptive drug treatment were 66+/-7%, 73+/-9% and 88+/-8% for MPF4 (1.0 mmol/kg, p.o.), dipyrone (1.0 mmol/kg, p.o.) and morphine (0.026 mmol/kg, p.o.), respectively. The maximal inhibitions obtained with curative drug treatment were 53+/-9%, 83+/-7% and 84+/-7%, for MPF4, dipyrone and morphine, respectively. Unlike indomethacin, MPF4 did not induce gastric lesions at the dose that caused the highest antinociception (1.0 mmol/kg, p.o). The anti-allodynic action of MPF4, dipyrone and morphine was not associated with impairment of motor activity.


CONCLUSIONS
The results of the present study suggest that MPF4 represents a potential target for the development of new drugs to treat persistent inflammatory pain.
Milano
Julie
J
Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, UFSM, Camobi, CEP 97105-900, Santa Maria, RS, Brazil.
Rossato
Mateus F
MF
Oliveira
Sara M
SM
Drewes
Carine
C
Machado
Pablo
P
Beck
Paulo
P
Zanatta
Nilo
N
Martins
Marcos A P
MA
Mello
Carlos F
CF
Rubin
Maribel A
MA
Ferreira
Juliano
J
Bonacorso
Helio G
HG
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000150:complications; D004177:Dipyrone / Q000494:pharmacology / Q000627:therapeutic use; D005620:Freund's Adjuvant; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010149:Postoperative Pain / Q000188:drug therapy / Q000523:psychology; D004856:Postural Balance / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology
C534720:4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009292:Narcotic Antagonists; D011720:Pyrazoles; D009270:Naloxone; D009271:Naltrexone; D004177:Dipyrone; D009020:Morphine; D005620:Freund's Adjuvant; C055382:naltrindole; D007213:Indomethacin