Evidence map›Paper›PMID 24189487›Full record

ReviewPharmacology & therapeutics2014

The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence.

Jeffrey M Witkin, Michael A Statnick, Linda M Rorick-Kehn, John E Pintar, Michael Ansonoff, Yanyun Chen, R Craig Tucker, Roberto Ciccocioppo

Erratum issuedOpen access · greenAbstract readReview
In one paragraph

Review in Pharmacology & therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 98 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.

  1. Pooled it
  2. A Selective Nociceptin Receptor Antagonist to Treat Depression: Evidence from Preclinical and Clinical Studies.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016
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  6. Identification of a stress-sensitive endogenous opioid-containing neuronal population in the paranigral ventral tegmental area.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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  7. Review
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  11. Review
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  19. Review
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Jeffrey M WitkinLilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: jwitkin@lilly.com.
Michael A StatnickLilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA.
Linda M Rorick-KehnLilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA.
John E PintarUniversity of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, USA.
Michael AnsonoffUniversity of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, USA.
Yanyun ChenLilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA.
R Craig TuckerLilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA.
Roberto CiccocioppoSchool of Pharmacy, University of Camerino, Camerino, Italy.
Eli Lilly (United States) · USUniversità di Camerino · IT

Funding

The Nociceptin ORL1 System: Treatment Target for RelapseR01AA014351 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI Friedbert Weiss · 2004 to 2026
$7.3M
Gene-environment interaction: the brain CRF system in alcohol preferring msP ratsR01AA017447 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ROBERTO, MARISA · 2009 to 2013
$1.8M
NIAAA NIH HHS R01 AA014351NIAAA NIH HHS R01 AA017447
6 · The paper itself

Abstract

Nociceptin/Orphanin FQ (N/OFQ) is a 17 amino acid peptide that was deorphanized in 1995. The generation of specific agonists, antagonists and receptor deficient mice and rats has enabled progress in elucidating the biological functions of N/OFQ. Additionally, radio-imaging technologies have been advanced for investigation of this system in animals and humans. Together with traditional neurobehavioral techniques, these tools have been utilized to identify the biological significance of the N/OFQ system and its interacting partners. The present review focuses on the role of N/OFQ in the regulation of feeding, body weight homeostasis, stress, the stress-related psychiatric disorders of depression and anxiety, and in drug and alcohol dependence. 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. In particular, the literature data suggest that antagonism of NOP receptors will produce anti-obesity and antidepressant activities in humans. However, there are also contradictory data discussed. The current literature on the role of N/OFQ in anxiety and addiction, on the other hand points primarily to a role of agonist modulation being potentially therapeutic. Some drug-like molecules that function either as agonists or antagonists of NOP receptors have been optimized for human clinical study to test some of these hypotheses. The discovery of PET ligands for NOP receptors, combined with the pharmacological tools and burgeoning preclinical data set discussed here bodes well for a rapid advancement of clinical understanding and potential therapeutic benefit.

Indexed as

Drug DesignAnimalsAnxietyHumansMiceMood DisordersNarcotic AntagonistsNociceptinNociceptin ReceptorObesityOpioid PeptidesRatsReceptors, OpioidStress, PsychologicalSubstance-Related DisordersNarcotic AntagonistsNociceptinNociceptin ReceptorOpioid PeptidesReceptors, Opioid(1S,3aS)-8- (2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one, a NOP receptor agonist2-{3-[1-((1R)-acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo-benzimidazol-1-yl}-N-methylacetamide, a NOP receptor agonist5-HT5-hydroxytryptamine or serotonin8-[bis(2-methylphenyl)-methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-olACTHadrenocorticotropic hormoneAlcohol-preferring ratsAnxietyBEDbed nucleus of stria terminalisbinge eating disorderBNSTCalcitonin gene related peptideCeAcentral nucleus of the amygdalaCGRP[(–)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol, a NOP receptor antagonistconditioned place preferenceconditioned taste aversioncorticotrophin-releasing factorCPPCRFCTADADepressiondopamineDrug dependenceendo-8-[bis(2-chlorophenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxamide, a NOP receptor agonistEPSCexcitatory post-synaptic currentforced-swim testFSTGIRKGPCRG-protein activated, inwardly rectifying K(+) channelG-protein-coupled receptorHPAhypothalamic–pituitary axisJ-113397JTC-801knockoutKOmajor depressive disorderMarchigian Sardinian Alcohol-PreferringMDDmedial prefrontal cortexmPFCmsPN-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide hydrochloride, a NOP receptor antagonistNAccNEneuropeptide YNociceptin opioid peptide or Nociceptin opioid peptide receptorNociceptin/Orphanin FQNociceptin/Orphanin FQ (F: phenylalanine, Q: glutamine, the amino acids that begin and end the peptide sequence)N/OFQNOPnorepinephrine[Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2), a NOP receptor antagonistNPYnucleus accumbensObesityopioid-receptor-likeORLPOMCP ratsPro-opiomelanocortinRo 64-6198SB-612111SCH 221510SCH 655842Stresstail-suspension test(±)trans-1-[1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one, a NOP receptor antagonistTSTUFP-101ventral tegmental areaVTAW212393

Identifiers

PMID24189487
PMCPMC5098338
OpenAlexW2002153331

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.