Khroyan Taline V, Polgar Willma E, Orduna Juan, Jiang Faming, Olsen Cris, Toll Lawrence, Zaveri Nurulain T
Center for Health Sciences, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
Eur J Pharmacol. 2009 May 21;610(1-3):49-54. doi: 10.1016/j.ejphar.2009.03.019. Epub 2009 Mar 12.
The effect of new NOP receptor agonists and antagonists in the rat chronic constriction injury model was investigated. Intraperitoneally administered NOP receptor agonist SR14150 and antagonists SR16430 and SR14148, had no effect on mechanical allodynia when given alone. The nonselective NOP/mu-opioid receptor agonist SR16435, however, produced an anti-allodynic response, similar to morphine and reversible by naloxone. Notably, co-administration of the NOP receptor antagonists potentiated the anti-allodynic activity of both morphine and SR16435. Increased levels of the NOP receptor are implicated in the reduced efficacy of morphine in neuropathic pain. Our results suggest the utility of NOP receptor antagonists for potentiating opioid efficacy in chronic pain.
研究了新型NOP受体激动剂和拮抗剂在大鼠慢性压迫性损伤模型中的作用。单独腹腔注射NOP受体激动剂SR14150以及拮抗剂SR16430和SR14148时，对机械性异常性疼痛没有影响。然而，非选择性NOP/μ-阿片受体激动剂SR16435产生了抗异常性疼痛反应，类似于吗啡，且可被纳洛酮逆转。值得注意的是，NOP受体拮抗剂的共同给药增强了吗啡和SR16435的抗异常性疼痛活性。NOP受体水平的升高与吗啡在神经性疼痛中的疗效降低有关。我们的结果表明，NOP受体拮抗剂在增强阿片类药物在慢性疼痛中的疗效方面具有实用性。
