Avaliação do potencial analgésico e anti-inflamatório do composto pirazólico 1,5-difenil-3-hidrazinopirazol(a) - DHP

Abstract

causing pain as a constant feature. The pyrazole compounds are the drugs of synthetic origin in their chemical structure consisting of a ring pirazolínico, with which several studies show the effectiveness in controlling of pain, fever and inflammation. The need to develop new drugs with analgesic and anti-inflammatory, low cost and which have few adverse reactions, has stimulated the synthesis and study of pharmacological activities of pyrazole compounds. With this objective, we studied the antinociceptive and anti-inflammatory potential of compound 1.5-diphenyl-pyrazole-3-hidrazinopirazol(a) (DHP), administered orally in pharmacological models of the acetic acid writhing, tail-flick, formalin, ear edema induced by croton oil and carrageenan-induced peritonitis in mice, and mechanical allodynia (von Frey) and thermal hyperalgesia (Hargreaves) in rats. The administration of DHP (1, 3 and 10mg/kg) decreased in a dose-dependent (41.3, 62.7 and 76%) number of writhing (ID50 = 1.3mg/kg). In the tail-flick test, DHP (10mg/kg) was ineffective and the application of positive control fentanyl (200μg/kg, sc) increased the latency to thermal stimulation in up to 138%. Without changing the first phase of nociception (neurogenic pain) of the formalin test, DHP (10mg/kg) and the positive control indomethacin (10mg/kg, p.o.) inhibited the reactivity in the 2 phase (ndinflammatory pain) in 40.9 and 48.7% respectively. This same dose of DHP reduced by 54% the ear edema induced by croton oil, as well as the positive control, dexamethasone (2mg/kg, sc) at 55.3%. Also in a dose-dependent DHP (3, 10 and 30 mg / kg) inhibited by 11.8, 39 and 53.7%, respectively, leukocyte migration in peritonitis induced by carrageenan test (ID50 = 22.9mg/kg). In the assessment of mechanical allodynia incision group treated with DHP (GIDHP - 10mg/kg) showed a significant reversal of allodynia (RA) after one hour of administration, with maximum reading RA for 12 hours (28.2%) in the second stage of the experiment, remaining in the third stage with RA of 26.9, 43.4 and 60.4% in the 7th, 10th and 14th days of evaluations, when compared with the vehicle group incised (GIV). In thermal hyperalgesia GIDHP (10mg/kg) also significantly reversed the hyperalgesia (RH) after one hour of treatment, with RH maximum of three hours in reading (68.9%) in the second stage, obtaining in the third stage RA of 43.4, 32,1 and 64% in 7th, 10th and 14th days of evaluations, when compared to the GIV and obtaining similar values of the group not incised vehicle (GNIV) on 14 dayth. In the von Frey and Hargreaves GNIV showed similar readings in the three stages of the experiment. The DHP (10mg/kg) did not alter the motor activity of mice in rota-rod test. Whereas the compound DHP showed antinociceptive activity in writhing test, antiedematogenic in ear edema, inhibited the 2nd phase of nociception (inflammatory pain) in formalin test and leukocyte migration, promoting reversal of hypernociception in models of thermal hyperalgesia and allodynia mechanics, these results indicate that the effectiveness of DHP involves the participation of anti-inflammatory mechanisms and create favorable outlook for its future use with this therapeutic goal.