- 作者：Julie Milano ; Mateus F. Rossato ; Sara M. Oliveira ; Carine Drewes ; Pablo Machado ; Paulo Beck ; Nilo Zanatta ; Marcos A.P. Martins ; Carlos F. Mello ; Maribel A. Rubin ; Juliano Ferreira ; Helio G. Bonacorso
- 关键词：Allodynia ; Inflammatory pain ; Pyrazoline methyl ester
- 刊名：Life Sciences
- 出版年：2008
- 出版时间：21 November 2008
- 年：2008
- 卷：83
- 期：21-22
- 页码：739-746
- 全文大小：642 K
AimsThe 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).Main 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.
Key findings
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.
Significance
The results of the present study suggest that MPF4 represents a potential target for the development of new drugs to treat persistent inflammatory pain.