SR 16435 [1-(1-(Bicyclo[3.3.1]nonan-9-yl)piperidin-4-yl)indolin-2-one], a Novel Mixed Nociceptin/Orphanin FQ/μ-Opioid Receptor Partial Agonist: Analgesic and Rewarding Properties in Mice

@article{Khroyan2007SR1,
  title={SR 16435 [1-(1-(Bicyclo[3.3.1]nonan-9-yl)piperidin-4-yl)indolin-2-one], a Novel Mixed Nociceptin/Orphanin FQ/$\mu$-Opioid Receptor Partial Agonist: Analgesic and Rewarding Properties in Mice},
  author={Taline V. Khroyan and Nurulain T. Zaveri and Willma E. Polgar and Juan Ordu{\~n}a and Cris M. Olsen and Faming Jiang and Lawrence Toll},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2007},
  volume={320},
  pages={934 - 943}
}
  • T. Khroyan, N. Zaveri, L. Toll
  • Published 1 February 2007
  • Biology, Psychology
  • Journal of Pharmacology and Experimental Therapeutics
We identified a novel nociceptin/orphanin FQ (NOP)/μ-opioid receptor agonist, SR 16435 [1-(1-(bicyclo[3.3.1]nonan-9-yl)piperidin-4-yl)indolin-2-one], with high binding affinity and partial agonist activity at both receptors. It was hypothesized that SR 16435 would produce antinociception and yet, unlike morphine, would have diminished rewarding properties and tolerance development. Antinociception was assessed in mice using the tail-flick assay, whereas behavioral and rewarding effects were… 
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The First Universal Opioid Ligand, (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028): Characterization of the In Vitro Profile and In Vivo Behavioral Effects in Mouse Models of Acute Pain and Cocaine-Induced Reward
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It is likely that with BU08028, a partial agonist at both NOP and receptors, -mediated activity overpowers NOPmediated effects, and that a different buprenorphine analog that is a universal high-affinity opioid ligand but with “full agonist” activity at NOP may counteract traditional opioidmediated effects such as antinociception and reward.
Differential Effects of Nociceptin/Orphanin FQ (NOP) Receptor Agonists in Acute versus Chronic Pain: Studies with Bifunctional NOP/μ Receptor Agonists in the Sciatic Nerve Ligation Chronic Pain Model in Mice
TLDR
Results indicate that, in mice, circuitry mediating antinociceptive activity in acute and chronic pain states is different, and that supraspinal up-regulation could lead to an attenuation of morphine ant inociception and antiallodynia, which can be alleviated by an NOP receptor antagonist.
Effects of Spinally Administered Bifunctional Nociceptin/Orphanin FQ Peptide Receptor/μ-Opioid Receptor Ligands in Mouse Models of Neuropathic and Inflammatory Pain
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Both NOP and MOP receptors in the spinal cord independently drive antinociception in mice, and spinally administered bifunctional NOP/MOP ligands not only can effectively attenuate neuropathic and inflammatory pain, but also have higher antiniceptive potency with reduced tolerance development to analgesia.
Pharmacological mechanisms underlying the antinociceptive and tolerance effects of the 6,14-bridged oripavine compound 030418
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The compound 030418 is a novel agonist of opioid receptors with high efficiency, long-lasting effect and liability to tolerance, which may be closely correlated with the methyl group at the N17 position and the high hydrophobicity of the C7-thiophene group in its chemical structure.
Comparison of the Antinociceptive and Antirewarding Profiles of Novel Bifunctional Nociceptin Receptor/μ-Opioid Receptor Ligands: Implications for Therapeutic Applications
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It is suggested that NOPr full-agonist activity is required to modulate opioid-induced reward, whereas a bifunctional Nopr/MOPr partial agonist profile may be suitable as a nonaddicting analgesic.
TH-030418: a potent long-acting opioid analgesic with low dependence liability
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The results indicate that TH-030418 is a potent long-acting opioid analgesic with low dependence liability and may be of some value in the development of new analgesics.
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Nociceptin/Orphanin FQ Receptor Activation Attenuates Antinociception Induced by Mixed Nociceptin/Orphanin FQ/μ-Opioid Receptor Agonists
TLDR
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 is supported.
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