Estudo dos mecanismos envolvidos no efeito antinociceptivo de uma fração de alcalóides oxindólicos de Uncaria tomentosa

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-Graduação em FarmacologiaUncaria tomentosa (Willd.) DC (Rubiaceae) is an indigenous plant of the Amazon rainforest, popularly known as cat#s claw. The medicinal use of this plant by Peruvian indians has drawn scientific interest over its healing propreties, and gave rise to an increasing number of studies about its biological activities. Chemically, the substances of greatest interest present in this plant are indole and oxindole alkaloids. This study characterizes the antinociceptive activity of a standardized fraction of oxindole alkaloids from U. tomentosa (UT) in mouse models of nociception. Pretreatment of animals with UT (3-300 mg/kg, i.p.) decreased, in a dose-dependent way, nociception elicited by chemical stimuli such as the intraperitoneal injection of acetic acid and the intraplantar injection of formalin, glutamate or capsaicin. Treatment with UT (300 mg/kg) significantly increased the latency of animals to respond to thermal noxious stimuli (hot plate and tail flick tests), probably revealing central effects of the alkaloids. Moreover, treatment with UT was able to inhibit nociceptive behavior caused by intratecal injection of glutamate, NMDA, substance P and the proinflammatory cytokines TNF-á and IL-1â. The antinociceptive effect of UT (100 mg/kg, i.p.) in the formalin test was abolished by pretreatment with ketanserin, an antagonist of serotonergic 5-HT2 receptors, but not by antagonists of the opioid receptors (naltrexone), muscarinic cholinergic receptors (atropine), or adrenergic á1 and á2 receptors (prazosin and yoimbine, respectively). In a similar way, pre-treatment with L-arginine, a substrate for the nitric oxide synthase enzyme, did not affect the antinociceptive activity of UT in the formalin test. These data suggest that the antinociceptive activity of UT involves an interaction with the serotonergic and the glutamatergic systems, but not with the other systems tested here