Khroyan TV, Polgar WE, Jiang F, Zaveri NT, Toll L
NOP Receptor Activation Attenuates Antinociception Induced by Mixed NOP/Mu-Opioid Receptor Agonists. [JOURNAL ARTICLE]
J Pharmacol Exp Ther 2009 Aug 27.
Activation of brain NOP receptors leads to attenuation of mu-opioid receptor-mediated (MOP receptor) antinociception. Buprenorphine, a high affinity partial MOP receptor agonist also binds to NOP receptors with 80 nM affinity. The buprenorphine-induced inverted U-shaped dose response curve for antinociception may be due to NOP receptor activation, given that in the presence of the NOP receptor antagonist, J113397, or in NOP receptor knockout mice, buprenorphine has a steeper dose response curve and acts as a full agonist. In order to further explore the involvement of the direct activation of NOP receptors by buprenorphine and other compounds that activate both NOP and MOP receptors, the antinociceptive effects of SR16435, SR16507, buprenorphine, pentazocine, and morphine, compounds with varying levels of MOP and NOP receptor affinity and efficacy, were assessed in mice using the tail-flick assay. The ability of the selective NOP receptor antagonist SB-612111 to potentiate antinociception induced by the above compounds was examined to investigate whether activation of NOP receptors leads to attenuation of MOP receptor-mediated antinociception. SB-612111 potentiated antinociception induced by buprenorphine and the other mixed NOP/MOP receptor agonists SR16435 and SR16507. However, SB-612111 had no effect on pentazocine or morphine antinociception, two compounds with no NOP receptor binding affinity. These results further support the hypothesis that activation of NOP receptors can lead to attenuation of MOP receptor-mediated antinociception elicited by mixed NOP/MOP receptor compounds such as buprenorphine, SR16435, and SR16507 and that, although low efficacy in vitro, buprenorphine has significant NOP receptor agonist activity in vivo.
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