Activities of Mixed NOP and μ-Opioid Receptor Ligands


Spagnolo, B., Calo, G., Polgar, W. E., Jiang, F., Olsen, C. M., Berzetei‐Gurske, I., … & Zaveri, N. T. (2008). Activities of mixed NOP and μ‐opioid receptor ligands. British journal of pharmacology, 153(3), 609-619.


Background and purpose:

Compounds that activate both NOP and μ-opioid receptors might be useful as analgesics and drug abuse medications. Studies were carried out to better understand the biological activity of such compounds.

Experimental approach:

Binding affinities were determined on membranes from cells transfected with NOP and opioid receptors. Functional activity was determined by [35S]GTPγS binding on cell membranes and using the mouse vas deferens preparation in vitro and the tail flick antinociception assay in vivo.

Key results:

Compounds ranged in affinity from SR14150, 20-fold selective for NOP receptors, to buprenorphine, 50-fold selective for μ-opioid receptors. In the [35S]GTPγS assay, SR compounds ranged from full agonist to antagonist at NOP receptors and most were partial agonists at μ-opioid receptors. Buprenorphine was a low efficacy partial agonist at μ-opioid receptors, but did not stimulate [35S]GTPγS binding through NOP. In the mouse vas deferens, each compound, except for SR16430, inhibited electrically induced contractions. In each case, except for N/OFQ itself, the inhibition was due to μ-opioid receptor activation, as determined by equivalent results in NOP receptor knockout tissues. SR14150 showed antinociceptive activity in the tail flick test, which was reversed by the opioid antagonist naloxone.

Conclusions and implications:

Compounds that bind to both μ-opioid and NOP receptors have antinociceptive activity but the relative contribution of each receptor is unclear. These experiments help characterize compounds that bind to both receptors, to better understand the mechanism behind their biological activities, and identify new pharmacological tools to characterize NOP and opioid receptors.

British Journal of Pharmacology (2008) 153, 609–619; doi:10.1038/sj.bjp.0707598; published online 3 December 2007

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