Antinociception induced by a novel alpha(2A) adrenergic receptor agonist in rodents acute and chronic pain models

作者:Sudo Roberto Takashi*; do Amaral Rachel Vieiralves; da Silva Monteiro Carlos Eduardo; Pitta Ivan da Rocha; Lima Maria do Carmo; Montes Guilherme Carneiro; Ririe Douglas Gordon; Hayashida Kenichiro; Zapata Sudo Gisele
来源:European Journal of Pharmacology, 2017, 815: 210-218.
DOI:10.1016/j.ejphar.2017.09.018

摘要

The mechanisms and antinociceptive effects of a novel alpha(2A) 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 a 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 10 mg/kg/d, p. o.), and those effects were attenuated by yohimbine (5 mg/kg), atropine (2 mg/kg), L-nitro arginine methyl ester (L-NAME; 30 mg/kg), or naloxone (2 mg/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.

  • 出版日期2017-11-15