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Antinociception induced by a novel α2A adrenergic receptor agonist in rodents acute and chronic pain models

2017; Elsevier BV; Volume: 815; Linguagem: Inglês

10.1016/j.ejphar.2017.09.018

1879-0712

Roberto T. Sudo, Rachel Vieiralves do Amaral, Carlos Eduardo da Silva Monteiro, Ivan da Rocha Pitta, Maria do Carmo Alves de Lima, Guilherme Carneiro Montes, Douglas G. Ririe, Ken–ichiro Hayashida, Gisele Zapata‐Sudo,

Neurotransmitter Receptor Influence on Behavior

The mechanisms and antinociceptive effects of a novel α2A adrenoceptor agonist, 3-(2-chloro-6-fluorobenzil)-imidazolinide-2,4-dione (PT-31) were investigated using animal models of acute and chronic pain. The effects of PT-31 on pain responses were examined using hot plate and formalin tests in mice and spinal nerve ligation (SNL)-induced hyperalgesia in rats. The effects of antagonists acting on α adrenoceptor were assessed to investigate the interaction of these pathways upon PT-31 induced antinociception. PT-31 effects on motor activity/skills and on hemodynamic parameters were also evaluated. PT-31 had dose-dependent antinociception effects on hot-plate and formalin-injection induced pain responses. Thermal hyperalgesia and mechanical allodynia were reduced following a 7 d treatment with PT-31 (1, 5, and 10mg/kg/d, p.o.), and those effects were attenuated by yohimbine (5mg/kg), atropine (2mg/kg), L-nitro arginine methyl ester (L-NAME; 30mg/kg), or naloxone (2mg/kg). In contrast to clonidine, PT-31 did not have locomotor or hemodynamic effects in rats. The present results suggest that PT-31 represents a candidate for pain treatment with advantages over clonidine, namely no locomotor or hemodynamic impairments.