Skip to main content
SpringerLink
Log in

Therapeutic Approaches for NOP Receptor Antagonists in Neurobehavioral Disorders: Clinical Studies in Major Depressive Disorder and Alcohol Use Disorder with BTRX-246040 (LY2940094)

  • Chapter
  • First Online:
Book cover The Nociceptin/Orphanin FQ Peptide Receptor

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 254))

Abstract

Conventional antidepressants increase the efflux of biogenic amine neurotransmitters (the monoamine hypothesis of depression) in the central nervous system (CNS) and are the principle drugs used to treat major depressive disorder (MDD). However, the lack of efficacy in some patients, the slow onset of action, and the side effect profiles of existing antidepressants necessitate the exploration of additional treatment options. The discovery of the nociceptin/orphanin FQ peptide NOP receptor (N/OFQ-NOP receptor) system and its characterization in preclinical biological and pharmacological stress-related conditions supports the potential antidepressant and anti-stress properties of a NOP receptor antagonist for the treatment of neurobehavioral disorders. BTRX-246040 (formerly LY2940094) was designed to test this hypothesis in the clinic. A small clinical proof of concept study demonstrated efficacy of BTRX-246040 in MDD patients. In this study, BTRX-246040 (40 mg, p.o.) significantly reduced negative bias as assessed by the facial recognition test within 1 week of treatment and decreased depression symptoms after 8 weeks. BTRX-246040 also reduced depression symptoms in a second trial with heavy alcohol drinkers. Given the comorbidity of MDD and alcohol use disorder, a compound with such effects in patients could be a valuable addition to the medications available. A proof of concept study showed efficacy of BTRX-246040 in reducing heavy drinking and increasing the probability of abstinence in individuals diagnosed with alcohol dependence. In addition, plasma levels of gamma-glutamyl transferase were decreased by BTRX-246040 compared to placebo control implying improvement in liver function. Collectively, the clinical data reviewed within this chapter suggest that BTRX-264040 functions to normalize dysfunction in reward circuits. The overall efficacy and safety of this compound with a novel mechanism of action are encouraging of further clinical development. BTRX-246040 is currently under development for MDD by BlackThorn Therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AUD:

Alcohol use disorder

BTRX-246040 = LY2940094:

[2-[4-[(2-chloro-4,4-difluoro-spiro[5Hthieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol

CGI-I:

Clinical Global Impression of Improvement

CGI-S:

Clinical Global Impression of Illness Severity

GRID-HAMD-17:

Grid format of the Hamilton Depression Rating Scale, 17 items

HADS:

Hospital Anxiety and Depression Scale

HAMA:

Hamilton Anxiety Rating Scale

LY2940094:

BTRX-246040

MADRS:

Montgomery-Asberg Depression Rating Scale

MDD:

Major depressive disorder

MPS:

Maier-Philipp subscale of the GRID-HAMD-17

N/OFQ:

Nociceptin/orphanin FQ

References

  • Argyropoulos SV, Nutt DJ (2013) Anhedonia revisited: is there a role for dopamine-targeting drugs for depression? J Psychopharmacol 27:869–877

    Article  CAS  PubMed  Google Scholar 

  • Beaulieu S, Saury S, Sareen J, Tremblay J, Schütz CG, McIntyre RS, Schaffer A (2012) Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force. Ann Clin Psychiatry 24:38–55

    PubMed  Google Scholar 

  • Berthele A, Platzer S, Dworzak D, Schadrack J, Mahal B, Büttner A, Assmus HP, Wurster K, Zieglgänsberger W, Conrad B, Tölle TR (2003) [3H]-nociceptin ligand-binding and nociceptin opioid receptor mrna expression in the human brain. Neuroscience 121(3):629–640

    Article  CAS  PubMed  Google Scholar 

  • Carvalho AF, Sharma MS, Brunoni AR, Vieta E, Fava GA (2016) The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother Psychosom 85(5):270–288

    Article  PubMed  Google Scholar 

  • Chiu M, Vigod S, Rahman F, Wilton AS, Lebenbaum M, Kurdyak P (2018) Mortality risk associated with psychological distress and major depression: a population-based cohort study. J Affect Disord 234:117–123

    Article  PubMed  Google Scholar 

  • Ciccocioppo R, Economidou D, Fedeli A, Massi M (2003) The nociceptin/orphanin FQ/NOP receptor system as a target for treatment of alcohol abuse: a review of recent work in alcohol-preferring rats. Physiol Behav 79(1):121–128

    Article  CAS  PubMed  Google Scholar 

  • Cranford JA, Nolen-Hoeksema S, Zucker RA (2011) Alcohol involvement as a function of co-occurring alcohol use disorders and major depressive episode: evidence from the national epidemiologic survey on alcohol and related conditions. Drug Alcohol Depend 117(2-3):145–151

    Article  PubMed  PubMed Central  Google Scholar 

  • de la Vega D, Piña A, Peralta FJ, Kelly SA, Giner L (2018) A review on the general stability of mood disorder diagnoses along the lifetime. Curr Psychiatry Rep 20:29

    Article  PubMed  Google Scholar 

  • Der-Avakian A, D’Souza MS, Potter DN, Chartoff EH, Carlezon WA Jr, Pizzagalli DA, Markou A (2017) Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats. Psychopharmacology 234:1603–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duman CH, Duman RS (2015) Spine synapse remodeling in the pathophysiology and treatment of depression. Neurosci Lett 601:20–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gavioli EC, Calo’ G (2013) Nociceptin/orphanin FQ receptor antagonists as innovative antidepressant drugs. Pharmacol Ther 140(1):10–25

    Article  CAS  PubMed  Google Scholar 

  • Gomez AF, Barthel AL, Hofmann SG (2018) Comparing the efficacy of benzodiazepines and serotonergic anti-depressants for adults with generalized anxiety disorder: a meta-analytic review. Expert Opin Pharmacother 19(8):883–894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, Pickering RP, Kaplan K (2004) Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 61:807–816

    Article  PubMed  Google Scholar 

  • Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, Pickering RP, Ruan J, Smith SM, Huang B, Hasin DS (2015) Epidemiology of DSM-5 alcohol use disorder results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiat 72:757–766

    Article  CAS  Google Scholar 

  • Gu H, Hu D, Hong XR, Mao J, Cui Y, Hui N et al (2003) Changes and significance of orphanin and serotonin in patients with postpartum depression. Zhonghua Fu Chan Ke Za Zhi 38:727–728

    PubMed  Google Scholar 

  • Hägele C, Schlagenhauf F, Rapp M, Sterzer P, Beck A, Bermpohl F, Stoy M, Ströhle A, Wittchen HU, Dolan RJ, Heinz A (2015) Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders. Psychopharmacology (Berl) 232(2):331–341

    Article  CAS  Google Scholar 

  • Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM (2004) Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry 161:1256–1263

    Article  PubMed  Google Scholar 

  • Harmer CJ, Cowen PJ, Goodwin GM (2011) Efficacy markers in depression. J Psychopharmacol 25:1148–1158

    Article  CAS  PubMed  Google Scholar 

  • Hieronymus F, Emilsson JF, Nilsson S, Eriksson E (2016) Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression. Mol Psychiatry 21(4):523–530

    Article  CAS  PubMed  Google Scholar 

  • Iversen L (2005) The monoamine hypothesis of depression. In: Licinio J, Wong ML (eds) Biology of depression. Wiley-VCH, Weinheim, pp 71–86

    Chapter  Google Scholar 

  • Jacobsen PL, Mahableshwarkar AR, Serenko M, Chan S, Trivedi MH (2015) A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with major depressive disorder. J Clin Psychiatry 76:575–582

    Article  PubMed  Google Scholar 

  • Jain R, Mahableshwarkar AR, Jacobsen PL (2013) A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder. Int J Neuropsychopharmacol 16:313–321

    Article  CAS  PubMed  Google Scholar 

  • Jansen L, van Schijndel M, van Waarde J, van Busschbach J (2018) Health-economic outcomes in hospital patients with medical-psychiatric comorbidity: a systematic review and meta-analysis. PLoS One 13(3):e0194029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kallupi M, Scuppa G, de Guglielmo G, Calò G, Weiss F, Statnick MA, Rorick-Kehn LM, Ciccocioppo R (2017) Genetic deletion of the nociceptin/orphanin FQ receptor in the rat confers resilience to the development of drug addiction. Neuropsychopharmacology 42(3):695–706

    Article  CAS  PubMed  Google Scholar 

  • Katz MM, Koslow SH, Frazer A (1996) Onset of antidepressant activity: reexamining the structure of depression and multiple actions of drugs. Depress Anxiety 4(6):257–267

    Article  PubMed  Google Scholar 

  • Katz MM, Tekell JL, Bowden CL, Brannan S, Houston JP, Berman N, Frazer A (2004) Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology 29(3):566–579

    Article  CAS  PubMed  Google Scholar 

  • Knowland D, Lim BK (2018) Circuit-based frameworks of depressive behaviors: the role of reward circuitry and beyond. Pharmacol Biochem Behav 174:42. https://doi.org/10.1016/j.pbb.2017.12.010. [Epub ahead of print]

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Koob GF (2015) The dark side of emotion: the addiction perspective. Eur J Pharmacol 753:73–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuzmin A, Madjid N, Johansson B, Terenius L, Ogren SO (2009) The nociceptin system and hippocampal cognition in mice: a pharmacological and genetic analysis. Brain Res 1305(Suppl):S7–S19

    Article  CAS  PubMed  Google Scholar 

  • Lambert C, Da Silva S, Ceniti AK, Rizvi SJ, Foussias G, Kennedy SH (2018) Anhedonia in depression and schizophrenia: a transdiagnostic challenge. CNS Neurosci Ther 24(7):615–623

    Article  PubMed  PubMed Central  Google Scholar 

  • Madrid A, Smith DG, Alvarez-Horine S, Saljooqi K, Dagum P, Mahableshwarkar A (2017) T122 assessing anhedonia with quantitative tasks and digital and patient reported measures in a multi-center, double-blind trial with BTRX-246040 for the treatment of major depressive disorder (NCT03193398). In American College of Neuropsychopharmacology 56th annual meeting, Palm Springs

    Google Scholar 

  • Mathews M, Gommoll C, Chen D, Nunez R, Khan A (2015) Efficacy and safety of vilazodone 20 and 40 mg in major depressive disorder: a randomized, double-blind, placebo controlled trial. Int Clin Psychopharmacol 30:67–74

    Article  PubMed  PubMed Central  Google Scholar 

  • Palpacuer C, Duprez R, Huneau A, Locher C, Boussageon R, Laviolle B, Naudet F (2018) Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate. Addiction 113(2):220–237

    Article  PubMed  Google Scholar 

  • Pan Z, Grovu RC, Cha DS, Carmona NE, Subramaniapillai M, Shekotikhina M, Rong C, Lee Y, McIntyre RS (2017) Pharmacological treatment of cognitive symptoms in major depressive disorder. CNS Neurol Disord Drug Targets 16(8):891–899

    PubMed  CAS  Google Scholar 

  • Peacock A, Leung J, Larney S, Colledge S, Hickman M, Rehm J, Giovino GA, West R, Hall W, Griffiths P, Ali R, Gowing L, Marsden J, Ferrari AJ, Grebely J, Farrell M, Degenhardt L (2018) Global statistics on alcohol, tobacco and illicit drug use: 2017 status report. Addiction 113(10):1905–1926

    Article  PubMed  Google Scholar 

  • Post A, Smart TS, Jackson K, Mann J, Mohs R, Rorick-Kehn L, Statnick M, Anton R, O’Malley SS, Wong CJ (2016a) Proof-of-concept study to assess the nociceptin receptor antagonist LY2940094 as a new treatment for alcohol dependence. Alcohol Clin Exp Res 40(9):1935–1944

    Article  CAS  PubMed  Google Scholar 

  • Post A, Smart TS, Krikke-Workel J, Dawson GR, Harmer CJ, Browning M, Jackson K, Kakar R, Mohs R, Statnick M, Wafford K, McCarthy A, Barth V, Witkin JM (2016b) A selective nociceptin receptor antagonist to treat depression: evidence from preclinical and clinical studies. Neuropsychopharmacology 41(10):1803–1812

    Article  CAS  PubMed  Google Scholar 

  • Price JL, Drevets WC (2012) Neural circuits underlying the pathophysiology of mood disorders. Trends Cogn Sci 16(1):61–71

    Article  PubMed  Google Scholar 

  • Raddad E, Chappell A, Meyer J, Wilson A, Ruegg CE, Tauscher J, Statnick MA, Barth V, Zhang X, Verfaille SJ (2016) Occupancy of nociceptin/orphanin FQ peptide receptors by the antagonist LY2940094 in rats and healthy human subjects. Drug Metab Dispos 44(9):1536–1542

    Article  CAS  PubMed  Google Scholar 

  • Rekik K, Faria Da Silva R, Colom M, Pacifico S, Zaveri NT, Calo’ G, Rampon C, Frances B, Mouledous L (2017) Activation of nociceptin/orphanin FQ receptors inhibits contextual fear memory reconsolidation. Neuropharmacology 125:39–49

    Article  CAS  PubMed  Google Scholar 

  • Repousi N, Masana MF, Sanchez-Niubo A, Haro JM, Tyrovolas S (2018) Depression and metabolic syndrome in the older population: a review of evidence. J Affect Disord 237:56–64

    Article  PubMed  Google Scholar 

  • Rorick-Kehn LM, Ciccocioppo R, Witkin JM, Adams BL, Katner JS, Perry KW, Toledo MA, Diaz N, Lafuente C, Jiménez A, Benito A, Martínez-Grau M, Pedregal-Tercero C, Statnick MA (2016) A novel, orally-bioavailable nociceptin receptor antagonist, LY2940094, reduces ethanol self-administration and ethanol-seeking in animal models. Alcoholism Clin Exp Res 40(5):945–954

    Article  CAS  Google Scholar 

  • Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D et al (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR_D report. Am J Psychiatry 163:1905–1917

    Article  PubMed  Google Scholar 

  • Sheiner LB (1997) Learning versus confirming in clinical drug development. Clin Pharmacol Ther 61:275–291

    Article  CAS  PubMed  Google Scholar 

  • Soyka M, Müller CA (2018) Pharmacotherapy of alcoholism – an update on approved and off-label medications. Expert Opin Pharmacother 18(12):1187–1199

    Article  CAS  Google Scholar 

  • Spampinato S, Baiula M, Calienni M (2007) Agonist-regulated internalization and desensitization of the human nociceptin receptor expressed in CHO cells. Curr Drug Targets 8(1):137–146

    Article  CAS  PubMed  Google Scholar 

  • Statnick MA, Chen Y, Ansonoff M, Witkin JM, Rorick-Kehn L, Suter TM, Song M, Hu C, Lafuente C, Jiménez A, Benito A, Diaz N, Martínez-Grau MA, Toledo MA, Pintar JE (2016) A novel nociceptin receptor antagonist LY2940094 inhibits excessive feeding behavior in rodents: a possible mechanism for the treatment of binge eating disorder. J Pharmacol Exp Ther 356(2):493–502

    Article  PubMed  Google Scholar 

  • Toledo MA, Pedregal C, Lafuente C, Diaz N, Martinez-Grau MA, Jiménez A, Benito A, Torrado A, Mateos C, Joshi EM, Kahl SD, Rash KS, Mudra DR, Barth VN, Shaw DB, McKinzie D, Witkin JM, Statnick MA, Toledo MA, Pedregal C, Lafuente C, Diaz N, Martinez-Grau MA, Jiménez A, Benito A, Torrado A, Mateos C, Joshi EM, Kahl SD, Rash KS, Mudra DR, Barth VN, Shaw DB, McKinzie D, Witkin JM, Statnick MA (2014) Discovery of a novel series of orally active nociceptin/orphanin FQ (NOP) receptor antagonists based on a dihydrospiro(piperidine-4,7′-thieno[2,3-c]pyran) scaffold. J Med Chem 57(8):3418–3429

    Article  CAS  PubMed  Google Scholar 

  • Tranter R, Bell D, Gutting P, Harmer C, Healy D, Anderson IM (2009) The effect of serotonergic and noradrenergic antidepressants on face emotion processing in depressed patients. J Affect Disord 118:87–93

    Article  CAS  PubMed  Google Scholar 

  • Ulbaldi M, Cannella N, Ciccocioppo R (2016) Emerging targets for addiction neuropharmacology: from mechanisms to therapeutics. Prog Brain Res 224:251–284

    Article  Google Scholar 

  • USDHHS (2015) Alcoholism: developing drugs for treatment – guidance for industry. Office of Communications, Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM433618.pdf

  • Vitale G, Filaferro M, Micioni Di Bonaventura MV, Ruggieri V, Cifani C, Guerrini R, Simonato M, Zucchini S (2017) Effects of [Nphe1, Arg14, Lys15] N/OFQ-NH2 (UFP-101), a potent NOP receptor antagonist, on molecular, cellular and behavioural alterations associated with chronic mild stress. J Psychopharmacol 31(6):691–703

    Article  CAS  PubMed  Google Scholar 

  • Wang LN, Liu LF, Zhang JX, Zhao GF (2009) Plasma levels of nociceptin/orphanin FQ in patients with bipolar disorders and healthy adults. Zhonghua Yi Xue Za Zhi 89:916–918

    PubMed  CAS  Google Scholar 

  • Witkin JM, Statnick MA, Rorick-Kehn LM, Pintar JE, Ansonoff M, Chen Y, Tucker RC, Ciccocioppo R (2014) The biology of nociceptin/orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence. Pharmacol Ther 141(3):283–299

    Article  CAS  PubMed  Google Scholar 

  • Witkin JM, Rorick-Kehn LM, Benvenga MJ, Adams BL, Gleason SD, Knitowski KM, Li X, Chaney S, Falcone JF, Smith JW, Foss J, Lloyd K, Catlow JT, McKinzie DL, Svensson KA, Barth VN, Toledo MA, Diaz N, Lafuente C, Jiménez A, Benito A, Pedregal C, Martínez-Grau MA, Post A, Ansonoff MA, Pintar JE, Statnick MA (2016) Preclinical findings predicting efficacy and side-effect profile of LY2940094, an antagonist of nociceptin receptors. Pharmacol Res Perspect 4(6):e00275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Witkin JM, Knutson DE, Rodriguez GJ, Shi S (2018) Rapid-acting antidepressants. Curr Pharm Des 24:2556–2563

    Article  CAS  PubMed  Google Scholar 

  • You C, Vandegrift B, Brodie MS (2018) Ethanol actions on the ventral tegmental area: novel potential targets on reward pathway neurons. Psychopharmacology 235(6):1711–1726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaveri NT (2016) Nociceptin opioid receptor (NOP) as a therapeutic target: progress in translation from preclinical research to clinical utility. J Med Chem 59(15):7011–7028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang LL, Zheng HP, Ma C, He ZG, Zheng CD (2009) The plasma orphanin FQ in patients with depression before and after treatment. Chin J Psychiatry 42:138–144

    CAS  Google Scholar 

  • Zimmerman M, Martinez JH, Young D, Chelminski I, Dalrymple K (2013) Severity classification on the Hamilton Depression Rating Scale. J Affect Disord 150:384–388

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the book editors for the invitation to review the data on BTRX-246040. JMW also thanks former colleagues with whom he had the pleasure and honor to work with in characterizing LY2940094 (now BTRX-246040). Specifically, he thanks Michael Statnick, Miguel Toledo, Linda Rorick-Kehn, Xia Li, Scott Gleason, Keith Wafford, and Vanessa Barth from Eli Lilly and Company (Indianapolis, Indiana, the USA, and Windlesham, Surrey, the UK), Roberto Ciccocioppo (University of Camerino, Italy), and John Pintar (Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA).

JMW dedicates this review to the memory of creative and energetic chemist, devoted humanitarian, and friend Conception Pedregal, who led the chemistry effort to discover BTRX-246040.

Conflict of Interest

WJM and TLW are employees of and shareholders in BlackThorn Therapeutics which is actively evaluating BTRX-246040 for the treatment of neurobehavioral disorders.

Author information

Authors and Affiliations

  1. Witkin Consulting Group, Carmel, IN, USA

    Jeffrey M. Witkin

  2. BlackThorn Therapeutics, San Francisco, CA, USA

    Tanya L. Wallace & William J. Martin

Authors
  1. Jeffrey M. Witkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tanya L. Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William J. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey M. Witkin .

Editor information

Editors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Winston-Salem, NC, USA

    Mei-Chuan Ko

  2. Department of Medical Sciences, Section of Pharmacology, University of Ferrara, Ferrara, Italy

    Girolamo Caló

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Witkin, J.M., Wallace, T.L., Martin, W.J. (2018). Therapeutic Approaches for NOP Receptor Antagonists in Neurobehavioral Disorders: Clinical Studies in Major Depressive Disorder and Alcohol Use Disorder with BTRX-246040 (LY2940094). In: Ko, MC., Caló, G. (eds) The Nociceptin/Orphanin FQ Peptide Receptor. Handbook of Experimental Pharmacology, vol 254. Springer, Cham. https://doi.org/10.1007/164_2018_186

Download citation

Publish with us

Policies and ethics

Search

Navigation