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The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence.
Pharmacol Ther 2014; 141(3):283-99P&T

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.

Authors+Show Affiliations

Lilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: jwitkin@lilly.com.Lilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA.Lilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA.University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, USA.University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, USA.Lilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA.Lilly Research Labs, Eli Lilly and Company, Indianapolis, IN, USA.School of Pharmacy, University of Camerino, Camerino, Italy.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

24189487

Citation

Witkin, Jeffrey M., et al. "The Biology of Nociceptin/Orphanin FQ (N/OFQ) Related to Obesity, Stress, Anxiety, Mood, and Drug Dependence." Pharmacology & Therapeutics, vol. 141, no. 3, 2014, pp. 283-99.
Witkin JM, Statnick MA, Rorick-Kehn LM, et al. The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence. Pharmacol Ther. 2014;141(3):283-99.
Witkin, J. M., Statnick, M. A., Rorick-Kehn, L. M., Pintar, J. E., Ansonoff, M., Chen, Y., ... Ciccocioppo, R. (2014). The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence. Pharmacology & Therapeutics, 141(3), pp. 283-99. doi:10.1016/j.pharmthera.2013.10.011.
Witkin JM, et al. The Biology of Nociceptin/Orphanin FQ (N/OFQ) Related to Obesity, Stress, Anxiety, Mood, and Drug Dependence. Pharmacol Ther. 2014;141(3):283-99. PubMed PMID: 24189487.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence. AU - Witkin,Jeffrey M, AU - Statnick,Michael A, AU - Rorick-Kehn,Linda M, AU - Pintar,John E, AU - Ansonoff,Michael, AU - Chen,Yanyun, AU - Tucker,R Craig, AU - Ciccocioppo,Roberto, Y1 - 2013/11/01/ PY - 2013/09/18/received PY - 2013/10/10/accepted PY - 2013/11/6/entrez PY - 2013/11/6/pubmed PY - 2014/9/16/medline KW - (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 agonist KW - (±)trans-1-[1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one, a NOP receptor antagonist KW - 2-{3-[1-((1R)-acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo-benzimidazol-1-yl}-N-methylacetamide, a NOP receptor agonist KW - 5-HT KW - 5-hydroxytryptamine or serotonin KW - 8-[bis(2-methylphenyl)-methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol KW - ACTH KW - Alcohol-preferring rats KW - Anxiety KW - BED KW - BNST KW - CGRP KW - CPP KW - CRF KW - CTA KW - Calcitonin gene related peptide KW - CeA KW - DA KW - Depression KW - Drug dependence KW - EPSC KW - FST KW - G-protein activated, inwardly rectifying K(+) channel KW - G-protein-coupled receptor KW - GIRK KW - GPCR KW - HPA KW - J-113397 KW - JTC-801 KW - KO KW - MDD KW - Marchigian Sardinian Alcohol-Preferring KW - N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide hydrochloride, a NOP receptor antagonist KW - N/OFQ KW - NAcc KW - NE KW - NOP KW - NPY KW - Nociceptin opioid peptide or Nociceptin opioid peptide receptor KW - Nociceptin/Orphanin FQ KW - Nociceptin/Orphanin FQ (F: phenylalanine, Q: glutamine, the amino acids that begin and end the peptide sequence) KW - ORL KW - Obesity KW - P rats KW - POMC KW - Pro-opiomelanocortin KW - Ro 64-6198 KW - SB-612111 KW - SCH 221510 KW - SCH 655842 KW - Stress KW - TST KW - UFP-101 KW - VTA KW - W212393 KW - [(–)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol, a NOP receptor antagonist KW - [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2), a NOP receptor antagonist KW - adrenocorticotropic hormone KW - bed nucleus of stria terminalis KW - binge eating disorder KW - central nucleus of the amygdala KW - conditioned place preference KW - conditioned taste aversion KW - corticotrophin-releasing factor KW - dopamine KW - endo-8-[bis(2-chlorophenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxamide, a NOP receptor agonist KW - excitatory post-synaptic current KW - forced-swim test KW - hypothalamic–pituitary axis KW - knockout KW - mPFC KW - major depressive disorder KW - medial prefrontal cortex KW - msP KW - neuropeptide Y KW - norepinephrine KW - nucleus accumbens KW - opioid-receptor-like KW - tail-suspension test KW - ventral tegmental area SP - 283 EP - 99 JF - Pharmacology & therapeutics JO - Pharmacol. Ther. VL - 141 IS - 3 N2 - 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. SN - 1879-016X UR - https://www.unboundmedicine.com/medline/citation/24189487/The_biology_of_Nociceptin/Orphanin_FQ__N/OFQ__related_to_obesity_stress_anxiety_mood_and_drug_dependence_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7258(13)00216-7 DB - PRIME DP - Unbound Medicine ER -