{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:40:55Z","timestamp":1790894455295,"version":"4.1.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100014653","name":"NIHR Manchester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pulmonary Pharmacology & Therapeutics"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1016\/j.pupt.2019.101853","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T11:55:54Z","timestamp":1571054154000},"page":"101853","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Emerging targets for cough therapies; NK1 receptor antagonists"],"prefix":"10.1016","volume":"59","author":[{"given":"Huda","family":"Badri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"15","key":"10.1016\/j.pupt.2019.101853_bib1","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1001\/archinte.158.15.1657","article-title":"Impact of chronic cough on quality of life","volume":"158","author":"French","year":"1998","journal-title":"Arch. Intern. Med."},{"key":"10.1016\/j.pupt.2019.101853_bib2","author":"PAoG"},{"issue":"6","key":"10.1016\/j.pupt.2019.101853_bib3","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1378\/chest.14-1481","article-title":"Anatomy and neurophysiology of cough: CHEST guideline and expert panel report","volume":"146","author":"Canning","year":"2014","journal-title":"Chest"},{"issue":"2","key":"10.1016\/j.pupt.2019.101853_bib4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.pupt.2009.01.003","article-title":"Central regulation of the cough reflex: therapeutic implications","volume":"22","author":"Canning","year":"2009","journal-title":"Pulm. Pharmacol. Ther."},{"issue":"4","key":"10.1016\/j.pupt.2019.101853_bib5","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1378\/chest.120.4.1121","article-title":"Application and validation of a computerized cough acquisition system for objective monitoring of acute cough: a meta-analysis","volume":"120","author":"Pavesi","year":"2001","journal-title":"Chest"},{"issue":"4","key":"10.1016\/j.pupt.2019.101853_bib6","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1152\/jappl.1990.68.4.1679","article-title":"Capsaicin-induced bronchoconstriction and neuropeptide release in Guinea pig perfused lungs","volume":"68","author":"Kroll","year":"1985","journal-title":"J. Appl. Physiol."},{"issue":"8475","key":"10.1016\/j.pupt.2019.101853_bib7","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0140-6736(86)90777-4","article-title":"Asthma as an axon reflex","volume":"1","author":"Barnes","year":"1986","journal-title":"Lancet"},{"key":"10.1016\/j.pupt.2019.101853_bib8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1471-2466-11-41","article-title":"Tachykinin receptors antagonism for asthma: a systematic review","volume":"11","author":"Ramalho","year":"2011","journal-title":"BMC Pulm. Med."},{"issue":"14","key":"10.1016\/j.pupt.2019.101853_bib9","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1056\/NEJMc0906670","article-title":"Aprepitant as an antipruritic agent?","volume":"361","author":"Duval","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.pupt.2019.101853_bib10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-3-662-44605-8_14","article-title":"NK-1 antagonists and itch","volume":"226","author":"Stander","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"issue":"4","key":"10.1016\/j.pupt.2019.101853_bib11","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2340\/00015555-3120","article-title":"Aprepitant in anti-histamine-refractory chronic nodular prurigo: a multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II trial (APREPRU)","volume":"99","author":"Tsianakas","year":"2019","journal-title":"Acta Derm. Venereol."},{"issue":"3","key":"10.1016\/j.pupt.2019.101853_bib12","first-page":"31","article-title":"Aprepitant (EMEND): the role of substance P in nausea and vomiting","volume":"19","author":"Prommer","year":"2005","journal-title":"J. Pain Palliat. Care Pharmacother."},{"issue":"3","key":"10.1016\/j.pupt.2019.101853_bib13","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2174\/1574887112666170406104854","article-title":"Rolapitant: an NK-1 receptor antagonist for the prevention of chemotherapy- induced nausea and vomiting","volume":"12","author":"Rapoport","year":"2017","journal-title":"Rev. Recent Clin. Trials"},{"key":"10.1016\/j.pupt.2019.101853_bib14","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jad.2017.07.042","article-title":"NK1 receptor antagonists for depression: why a validated concept was abandoned","volume":"223","author":"Rupniak","year":"2017","journal-title":"J. Affect. Disord."},{"issue":"1","key":"10.1016\/j.pupt.2019.101853_bib15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0304-3959(91)90015-P","article-title":"Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of N-methyl-D-aspartic acid and substance P","volume":"47","author":"Dougherty","year":"1991","journal-title":"Pain"},{"issue":"3","key":"10.1016\/j.pupt.2019.101853_bib16","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0304-3959(91)90100-C","article-title":"The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states","volume":"44","author":"Woolf","year":"1991","journal-title":"Pain"},{"issue":"4","key":"10.1016\/j.pupt.2019.101853_bib17","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/j.1460-9568.2008.06378.x","article-title":"Extended secondhand tobacco smoke exposure induces plasticity in nucleus tractus solitarius second-order lung afferent neurons in young Guinea pigs","volume":"28","author":"Sekizawa","year":"2008","journal-title":"Eur. J. Neurosci."},{"issue":"4","key":"10.1016\/j.pupt.2019.101853_bib18","doi-asserted-by":"crossref","first-page":"R1215","DOI":"10.1152\/ajpregu.2000.279.4.R1215","article-title":"Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output","volume":"279","author":"Mutoh","year":"2000","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"issue":"Pt 2","key":"10.1016\/j.pupt.2019.101853_bib19","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1113\/jphysiol.2005.093153","article-title":"Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in Guinea-pigs","volume":"569","author":"Mazzone","year":"2005","journal-title":"J. Physiol."},{"issue":"4","key":"10.1016\/j.pupt.2019.101853_bib20","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.pupt.2006.10.013","article-title":"Air pollutants and cough","volume":"20","author":"Joad","year":"2007","journal-title":"Pulm. Pharmacol. Ther."},{"issue":"2","key":"10.1016\/j.pupt.2019.101853_bib21","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/sj.bjp.0701111","article-title":"Central antitussive activity of the NK1 and NK2 tachykinin receptor antagonists, CP-99,994 and SR 48968, in the Guinea-pig and cat","volume":"121","author":"Bolser","year":"1997","journal-title":"Br. J. Pharmacol."},{"issue":"3","key":"10.1016\/j.pupt.2019.101853_bib22","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1152\/jappl.1999.86.3.1017","article-title":"Influence of central antitussive drugs on the cough motor pattern","volume":"86","author":"Bolser","year":"1985","journal-title":"J. Appl. Physiol."},{"issue":"1\u20133","key":"10.1016\/j.pupt.2019.101853_bib23","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ejphar.2003.11.048","article-title":"Antitussive activity of the tachykinin NK1 receptor antagonist, CP-99994, in dogs","volume":"485","author":"Chapman","year":"2004","journal-title":"Eur. J. Pharmacol."},{"issue":"1","key":"10.1016\/j.pupt.2019.101853_bib24","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1164\/ajrccm.158.1.9705052","article-title":"Involvement of tachykinin NK3 receptors in citric acid-induced cough and bronchial responses in Guinea pigs","volume":"158","author":"Daoui","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"1","key":"10.1016\/j.pupt.2019.101853_bib25","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1124\/jpet.300.1.314","article-title":"Nonpeptide tachykinin receptor antagonists. III. SB 235375, a low central nervous system-penetrant, potent and selective neurokinin-3 receptor antagonist, inhibits citric acid-induced cough and airways hyper-reactivity in Guinea pigs","volume":"300","author":"Hay","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"1","key":"10.1016\/j.pupt.2019.101853_bib26","doi-asserted-by":"crossref","first-page":"R243","DOI":"10.1152\/ajpregu.00184.2008","article-title":"Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit","volume":"295","author":"Mutolo","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"10.1016\/j.pupt.2019.101853_bib27","series-title":"The British Thoracic Society Meeting","first-page":"S114","article-title":"A double blind, placebo controlled, randomised, study to assess the effects of placebo, codeine and talnetant, on citric acid and cough threshold in healthy subjects","author":"Khalid","year":"2010"},{"key":"10.1016\/j.pupt.2019.101853_bib28","series-title":"The American Thoracic Society Meeting","article-title":"DNK33 a dual NK1\/NK2 receptor antagonist does not inhibit cough in COPD","author":"Pascoe","year":"2007"},{"issue":"3","key":"10.1016\/j.pupt.2019.101853_bib29","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1164\/ajrccm.152.3.7663799","article-title":"Effect of an NK1 receptor antagonist (CP-99,994) on hypertonic saline-induced bronchoconstriction and cough in male asthmatic subjects","volume":"152","author":"Fahy","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"12","key":"10.1016\/j.pupt.2019.101853_bib30","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1164\/rccm.201508-1602OC","article-title":"Neurophenotypes in airway diseases. Insights from translational cough studies","volume":"193","author":"Belvisi","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"1","key":"10.1016\/j.pupt.2019.101853_bib31","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jaci.2014.01.038","article-title":"Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial","volume":"134","author":"Khalid","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"issue":"10","key":"10.1016\/j.pupt.2019.101853_bib32","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1164\/rccm.201704-0769OC","article-title":"XEN-D0501, a novel transient receptor potential vanilloid 1 antagonist, does not reduce cough in patients with refractory cough","volume":"196","author":"Belvisi","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"suppl 60","key":"10.1016\/j.pupt.2019.101853_bib33","first-page":"PA3547","article-title":"Neurokinin-1 receptor antagonism for the treatment of cough in lung cancer","volume":"48","author":"Harle","year":"2016","journal-title":"Eur. Respir. J."},{"issue":"10S","key":"10.1016\/j.pupt.2019.101853_bib34","doi-asserted-by":"crossref","first-page":"S360","DOI":"10.1016\/j.jtho.2018.08.327","article-title":"Aprepitant for cough suppression in advanced lung cancer: a randomized trial [abstract]","volume":"13","author":"Prabhash VN","year":"2018","journal-title":"J. Thorac. Oncol."},{"issue":"5","key":"10.1016\/j.pupt.2019.101853_bib35","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1177\/0269881113480990","article-title":"Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies","volume":"27","author":"Ratti","year":"2013","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.pupt.2019.101853_bib36","first-page":"A2672","article-title":"The neurokinin-1 receptor antagonist orvepitant is a novel anti-tussive therapy for chronic refractory cough: results from a phase 2 study (VOLCANO-1)","volume":"195","author":"Smith","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.pupt.2019.101853_bib37","series-title":"A Dose-Ranging Study of Orvepitant in Patients with Chronic Refractory Cough [Internet]","year":"2016"},{"issue":"2","key":"10.1016\/j.pupt.2019.101853_bib38","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.juro.2010.03.147","article-title":"A multicenter, double-blind, randomized, placebo controlled trial of a neurokinin-1 receptor antagonist for overactive bladder","volume":"184","author":"Frenkl","year":"2010","journal-title":"J. Urol."},{"issue":"5","key":"10.1016\/j.pupt.2019.101853_bib39","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/j.jaad.2019.01.052","article-title":"Serlopitant reduced pruritus in patients with prurigo nodularis in a phase 2, randomized, placebo-controlled trial","volume":"80","author":"Stander","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"issue":"5","key":"10.1016\/j.pupt.2019.101853_bib40","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.jaad.2018.02.030","article-title":"Serlopitant for the treatment of chronic pruritus: results of a randomized, multicenter, placebo-controlled phase 2 clinical trial","volume":"78","author":"Yosipovitch","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"10.1016\/j.pupt.2019.101853_bib41","series-title":"Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Refractory Chronic Cough","year":"2017"},{"key":"10.1016\/j.pupt.2019.101853_bib42","series-title":"Menlo Therapeutics Announces Results from a Phase 2 Clinical Trial of Serlopitant for the Treatment of Refractory Chronic Cough","year":"2018"},{"issue":"10","key":"10.1016\/j.pupt.2019.101853_bib43","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/S2213-2600(17)30310-7","article-title":"A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial","volume":"5","author":"Birring","year":"2017","journal-title":"Lancet Respir Med"},{"issue":"6","key":"10.1016\/j.pupt.2019.101853_bib44","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1097\/JCP.0b013e31823608ca","article-title":"Results from 2 randomized, double-blind, placebo-controlled studies of the novel NK1 receptor antagonist casopitant in patients with major depressive disorder","volume":"31","author":"Ratti","year":"2011","journal-title":"J. Clin. Psychopharmacol."},{"issue":"12","key":"10.1016\/j.pupt.2019.101853_bib45","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.5665\/sleep.3208","article-title":"Efficacy of vestipitant, a neurokinin-1 receptor antagonist, in primary insomnia","volume":"36","author":"Ratti","year":"2013","journal-title":"Sleep"},{"issue":"9974","key":"10.1016\/j.pupt.2019.101853_bib46","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/S0140-6736(14)61255-1","article-title":"P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study","volume":"385","author":"Abdulqawi","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.pupt.2019.101853_bib47","first-page":"A6524","article-title":"A phase 2 dose-escalation study with af-219, a P2X3 antagonist for the treatment of chronic cough","volume":"193","author":"Smith JAK","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.pupt.2019.101853_bib48","first-page":"A7608","article-title":"MK-7264, a P2X3 receptor antagonist, reduces cough frequency in patients with refractory chronic cough: results from a randomized, controlled, phase 2b clinical trial","volume":"195","author":"Smith","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.pupt.2019.101853_bib49","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1745-9974-5-10","article-title":"Associations of physical and mental health problems with chronic cough in a representative population cohort","volume":"5","author":"Adams","year":"2009","journal-title":"Cough"}],"container-title":["Pulmonary Pharmacology & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1094553919301026?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1094553919301026?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T21:28:51Z","timestamp":1761082131000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1094553919301026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":49,"alternative-id":["S1094553919301026"],"URL":"https:\/\/doi.org\/10.1016\/j.pupt.2019.101853","relation":{},"ISSN":["1094-5539"],"issn-type":[{"value":"1094-5539","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Emerging targets for cough therapies; NK1 receptor antagonists","name":"articletitle","label":"Article Title"},{"value":"Pulmonary Pharmacology & Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pupt.2019.101853","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"101853"}}