Activity of new NOP receptor ligands in a rat peripheral mononeuropathy model: potentiation of morphine anti-allodynic activity by NOP receptor antagonists.
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.
Khroyan
Taline V
TV
Center for Health Sciences, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
Polgar
Willma E
WE
Orduna
Juan
J
Jiang
Faming
F
Olsen
Cris
C
Toll
Lawrence
L
Zaveri
Nurulain T
NT
D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008024:Ligands; D008297:Male; D020422:Mononeuropathies / Q000188:drug therapy* / Q000209:etiology; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D043803:Phenalenes / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000502:physiology; D012584:Sciatic Nerve / Q000601:surgery; D000094942:Nociceptin Receptor
D000701:Analgesics, Opioid; D007211:Indoles; D008024:Ligands; D009020:Morphine; D043803:Phenalenes; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D000094942:Nociceptin Receptor; C583123:1-(1-(2,3,3alpha,4,5,6-hexahydro-1H-phenalen-1-yl)piperidin-4-yl)indolin-2-one; C000722285:Oprl1 protein, rat