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Eur J Pharmacol. 2017 Nov 15;815:210-218. doi: 10.1016/j.ejphar.2017.09.018. Epub 2017 Sep 19.

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

Author information

1
Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brazil. Electronic address: rtakashisudo@gmail.com.
2
Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brazil.
3
Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, PE, Brazil.
4
Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
5
Department of Neurophysiology, Akita University School of Medicine, Akita, Japan.

Abstract

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.

KEYWORDS:

Acute and chronic pain; Clonidine; Locus coeruleus; PT-31; α(2A) adrenoceptors

PMID:
28935564
DOI:
10.1016/j.ejphar.2017.09.018
[Indexed for MEDLINE]

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