The anxiolytic-like profile of the nociceptin receptor agonist, endo-8-[bis(2-chlorophenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxamide (SCH 655842): comparison of efficacy and side effects across rodent species.

@article{Lu2011TheAP,
  title={The anxiolytic-like profile of the nociceptin receptor agonist, endo-8-[bis(2-chlorophenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxamide (SCH 655842): comparison of efficacy and side effects across rodent species.},
  author={Sherry Lu and Guy A Higgins and Robert A. Hodgson and Lynn A. Hyde and Robert A Del Vecchio and Donald H. Guthrie and Tatiana M. Kazdoba and Martha F. McCool and Cynthia A. Morgan and Ana Bercovici and Ginny D. Ho and Deen Bandhu Tulshian and Eric M. Parker and John C. Hunter and Geoffrey B. Varty},
  journal={European journal of pharmacology},
  year={2011},
  volume={661 1-3},
  pages={
          63-71
        }
}
The endogenous opioid-like peptide, nociceptin, produces anxiolytic-like effects that are mediated via the nociceptin (NOP) receptor. Similarly, synthetic, non-peptide NOP agonists produce robust anxiolytic-like effects although these effects are limited by marked side effects. In the present studies, the effects of a novel NOP receptor agonist, SCH 655842, were examined in rodent models sensitive to anxiolytic drugs and tests measuring potential adverse affects. Oral administration of SCH… 
Beta-arrestin 2 rather than G protein efficacy determines the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands
TLDR
The results suggest that the action of a NOP ligand on emotional states is better predicted based on its β-arrestin 2 rather than G-protein efficacy.
Functional antagonism between nociceptin/orphanin FQ and corticotropin-releasing factor in rat anxiety-related behaviors: Involvement of the serotonergic system
TLDR
The present study confirms that N/OFQ counteracts CRF anxiogenic-like effects in the behavioral tests evaluated, which support the hypothesis that N /OFQ may behave as functional CRF antagonist, this action being of interest for the treatment of anxiety disorders.
Characterization of a novel vasopressin V1b receptor antagonist, V1B-30N, in animal models of anxiety-like and depression-like behavior.
TLDR
Results suggest that acute pharmacological antagonism of the V1b receptor has anxiolytic-like but not antidepressant-like properties, which is consistent with previous findings with other V 1b antagonists.
The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence.
TLDR
Critical evaluation of the current scientific preclinical literature suggests that small molecule modulators of nociceptin opioid peptide receptors (NOP) might be useful in the treatment of diseases related to these biological functions and that antagonism of NOP receptors will produce anti-obesity and antidepressant activities in humans.
Functional plasticity of the N/OFQ‐NOP receptor system determines analgesic properties of NOP receptor agonists
TLDR
In rodents, systemically administered NOP receptor agonists exerted antihypersensitive effects in models of neuropathic and inflammatory pain, but they were largely ineffective in acute pain while concomitantly evoking severe motor side effects.
Blockade of NOP receptor modulates anxiety-related behaviors in mice exposed to inescapable stress
TLDR
Helpless mice displayed increased anxiety compared to non-stressed and non-helpless animals, thus supporting use of this approach as an animal model to investigate anxiety/depression comorbidity.
NOP Ligands for the Treatment of Anxiety and Mood Disorders.
TLDR
This chapter summarized the most relevant findings of NOP receptor ligands in the modulation of anxiety and mood disorders, and the putative mechanisms of action are discussed.
Nociceptin/orphanin FQ peptide receptor antagonist JTC‐801 reverses pain and anxiety symptoms in a rat model of post‐traumatic stress disorder
TLDR
The effect of JTC‐801, a nociceptin/orphanin FQ peptide (NOP) receptor antagonist, is determined on symptoms of pain and anxiety in rats after SPS exposure and the N/OFQ‐NOP receptor system changes are examined.
Nociceptin Opioid Receptor (NOP) as a Therapeutic Target: Progress in Translation from Preclinical Research to Clinical Utility.
  • N. Zaveri
  • Medicine, Chemistry
    Journal of medicinal chemistry
  • 2016
TLDR
The progress toward validating the NOP-N/OFQ system as a therapeutic target is discussed, suggesting that NOP agonists may have clinical utility for pain treatment and substance abuse pharmacotherapy.
Role of nociceptin/orphanin FQ in thermoregulation
TLDR
Critical evaluation of the literature data suggests that N/OFQ, acting through the NOP receptor, may cause hypothermia by influencing the complex thermoregulatory system that operates as a federation of independent thermoeffector loops to control body temperature at the hypothalamic level.
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References

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The Anxiolytic-Like Effects of the Novel, Orally Active Nociceptin Opioid Receptor Agonist 8-[bis(2-Methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)
TLDR
The data suggest that NOP agonists such as SCH 221510 may have an anxiolytic-like profile similar to benzodiazepines, with a reduced side-effect liability.
Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species
TLDR
The findings of this study confirm the potent, ORL-1 receptor-mediated, anxiolytic-like effects of Ro64-6198, extending the findings across three species.
Pharmacological characterization of the newly synthesized nociceptin/orphanin FQ-receptor agonist 1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-[(3R)-3-piperidinyl]-1H-benzimidazole as an anxiolytic agent.
TLDR
The findings suggest that MCOPPB - a compound with few adverse effects on the central nervous system - is a potential therapeutic agent for the treatment of anxiety.
Pharmacological properties of a novel nociceptin/orphanin FQ receptor agonist, 2-(3,5-dimethylpiperazin-1-yl)-1-[1-(1-methylcyclooctyl)piperidin-4-yl]-1H-benzimidazole, with anxiolytic potential.
TLDR
The results indicate that PCPB is a potent anxiolytic agent with agonistic activities for the NOP receptor with central effects of PCPB were weak.
A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat.
TLDR
These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ/nociceptin neuropeptide given locally into the brain and support a role for orphan in F Q/nOCiceptin in adaptive behavioral fear responses to stress.
Behavioral Effects of a Synthetic Agonist Selective for Nociceptin/Orphanin FQ Peptide Receptors in Monkeys
TLDR
These results provide the first functional evidence that the activation of NOP receptors produces antinociception without reinforcing effects in primates.
The effects of nociceptin/orphanin FQ receptor agonist Ro 64-6198 and diazepam on antinociception and remifentanil self-administration in rhesus monkeys
TLDR
The findings suggest that the effects of Ro 64-6198 on operant lever pressing are mediated by NOP receptors and that larger doses are required to impact operant behavior when compared directly with those that produce antinociception.
Long-lasting antinociceptive spinal effects in primates of the novel nociceptin/orphanin FQ receptor agonist UFP-112
TLDR
This study is the first to provide functional evidence that selective NOP receptor agonists such as UFP‐112 alone or in conjunction with morphine may improve the quality of spinal analgesia.
Pharmacological characterization of the novel nonpeptide orphanin FQ/nociceptin receptor agonist Ro 64-6198: rapid and reversible desensitization of the ORL1 receptor in vitro and lack of tolerance in vivo.
TLDR
Data show that nonpeptide agonists at the ORL1 receptor have a good clinical potential as anxiolytics without causing tolerance, and Ro 64-6198 was able to reduce brain OrL1 binding sites in both acutely and chronically treated rats.
Influence of the selective ORL1 receptor agonist, Ro64-6198, on rodent neurological function
TLDR
Results confirm Ro64-6198 to be a highly selective pharmacological tool to investigate ORL1 receptor function in vivo and, furthermore, that activation of this receptor is accompanied by a variety of effects on neurological function.
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