{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T20:50:56Z","timestamp":1775249456741,"version":"3.50.1"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T00:00:00Z","timestamp":1423699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T00:00:00Z","timestamp":1423699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Clin Pharm"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>\n            <jats:italic>Background<\/jats:italic>: Currently available over-the-counter cough remedies historically have been criticized for lack of scientific evidence supporting their efficacy. Although the first-generation antihistamine diphenhydramine is classified as an antitussive by the United States Food and Drug Administration, to the authors\u2019 knowledge it has never been shown to inhibit cough reflex sensitivity in subjects with pathological cough. <jats:italic>Objective<\/jats:italic>: To evaluate the effect of diphenhydramine on cough reflex sensitivity. <jats:italic>Setting<\/jats:italic>: Montefiore Medical Center, an academic medical center in New York City. <jats:italic>Methods<\/jats:italic>: Twenty two subjects with acute viral upper respiratory tract infection (common cold) underwent cough reflex sensitivity measurement employing capsaicin challenge on 3\u00a0separate days, 2\u00a0h after ingesting single doses of study drug (to coincide with peak blood concentrations), administered in randomized, double-blind manner: a multicomponent syrup containing diphenhydramine (25\u00a0mg), phenylephrine (10\u00a0mg), in a natural cocoa formulation; dextromethorphan (30\u00a0mg) syrup; and, placebo syrup. The standard endpoint of cough challenge was used: concentration of capsaicin inducing \u22655 coughs (C5). <jats:italic>Main outcome measure<\/jats:italic>: Effect on cough reflex sensitivity (C5). <jats:italic>Results<\/jats:italic>: A significant difference (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0024) was established among groups, with pairwise analysis revealing a significant increase in mean log C5 (0.4\u00a0\u00b1\u00a00.55 (SD); <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01) for the diphenhydramine-containing medication versus placebo, but not for dextromethorphan versus placebo. <jats:italic>Conclusions<\/jats:italic>: Our results provide the initial evidence of the ability of diphenhydramine to inhibit cough reflex sensitivity in subjects with acute pathological cough. Timing of cough reflex sensitivity measurement may not have allowed demonstration of maximal antitussive effect of dextromethorphan.<\/jats:p>","DOI":"10.1007\/s11096-015-0081-8","type":"journal-article","created":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T04:27:24Z","timestamp":1423628844000},"page":"471-474","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of cough reflex sensitivity by diphenhydramine during acute viral respiratory tract infection"],"prefix":"10.1007","volume":"37","author":[{"given":"Peter V.","family":"Dicpinigaitis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Dhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Gayle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Brew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilson","family":"Caparros-Wanderley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,2,12]]},"reference":[{"key":"81_CR1","unstructured":"Hsiao C-J, Cherry DK, Beatty PC, Rechtsteiner E. National ambulatory medical care survey: 2007 summary. National Health Statistics Reports; No. 27. Hyatsville: National Center for Health Statistics. 2010."},{"key":"81_CR2","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1124\/pr.111.005116","volume":"66","author":"PV Dicpinigaitis","year":"2014","unstructured":"Dicpinigaitis PV, Morice AH, Birring SS, McGarvey L, Smith JA, Canning BJ, et al. Antitussive drugs-past, present, and future. Pharmacol Rev. 2014;66:468\u2013512.","journal-title":"Pharmacol Rev"},{"key":"81_CR3","first-page":"30042","volume":"52","author":"Department of Health and Human Services. Food and Drug Administration","year":"1987","unstructured":"Department of Health and Human Services. Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; final monograph for OTC antitussive drug products. Fed Regist. 1987;52:30042\u201357.","journal-title":"Fed Regist"},{"key":"81_CR4","first-page":"29172","volume":"59","author":"Department of Health and Human Services. Food and Drug Administration","year":"1994","unstructured":"Department of Health and Human Services. Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; amendment of final monograph for OTC antitussive drug products. Fed Regist. 1994;59:29172\u20134.","journal-title":"Fed Regist"},{"key":"81_CR5","first-page":"218","volume":"29","author":"EW Packman","year":"1991","unstructured":"Packman EW, Ciccone PE, Wilson J, Masurat T. Antitussive effects of diphenhydramine on the citric acid aerosol-induced cough response in humans. Int J Clin Pharmacol Ther Toxicol. 1991;29:218\u201322.","journal-title":"Int J Clin Pharmacol Ther Toxicol"},{"key":"81_CR6","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/cpt1976194421","volume":"19","author":"LS Lilienfield","year":"1976","unstructured":"Lilienfield LS, Rose JC, Princiotto JV. Antitussive activity of diphenhydramine in chronic cough. Clin Pharmacol Ther. 1976;19:421\u20135.","journal-title":"Clin Pharmacol Ther"},{"issue":"Suppl 1","key":"81_CR7","doi-asserted-by":"publisher","first-page":"1S","DOI":"10.1378\/chest.129.1_suppl.1S","volume":"129","author":"RS Irwin","year":"2006","unstructured":"Irwin RS, Baumann MH, Bolser DC, Boulet L-P, Braman SS, Brightling CE, et al. Diagnosis and management of cough: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(Suppl 1):1S\u2013292S.","journal-title":"Chest"},{"key":"81_CR8","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s11096-007-9122-2","volume":"29","author":"I Bjornsdottir","year":"2007","unstructured":"Bjornsdottir I, Einarson TR, Gudmundsson LS, Einarsdottir RA. Efficacy of diphenhydramine against cough in humans: a review. Pharm World Sci. 2007;29:577\u201383.","journal-title":"Pharm World Sci"},{"key":"81_CR9","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1183\/09031936.00101006","volume":"29","author":"AH Morice","year":"2007","unstructured":"Morice AH, Fontana GA, Belvisi MG, Birring SS, Chung KF, Dicpinigaitis PV, et al. European Respiratory Society Task Force. ERS guidelines on the assessment of cough. Eur Respir J. 2007;29:1256\u201376.","journal-title":"Eur Respir J"},{"key":"81_CR10","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1745-9974-8-10","volume":"8","author":"PV Dicpinigaitis","year":"2012","unstructured":"Dicpinigaitis PV. Review: effect of drugs on human cough reflex sensitivity to inhaled capsaicin. Cough. 2012;8:10.","journal-title":"Cough"},{"key":"81_CR11","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.pupt.2014.05.004","volume":"28","author":"PV Dicpinigaitis","year":"2014","unstructured":"Dicpinigaitis PV, Tibb AS, Ramsey DL, Carr AN, Poore CL. Stability of cough reflex sensitivity during viral upper respiratory tract infection (common cold). Pulm Pharmacol Ther. 2014;28:154\u20137.","journal-title":"Pulm Pharmacol Ther"},{"key":"81_CR12","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1002\/j.1552-4604.1986.tb02946.x","volume":"26","author":"GT Blyden","year":"1986","unstructured":"Blyden GT, Greenblatt DJ, Scavone JM, Shader RI. Pharmacokinetics of diphenhydramine and a demethylated metabolite following intravenous and oral administration. J Clin Pharmacol. 1986;26:529\u201333.","journal-title":"J Clin Pharmacol"},{"key":"81_CR13","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S0009-9236(96)90056-9","volume":"60","author":"DA Capon","year":"1996","unstructured":"Capon DA, Bochner F, Kerry N, Mikus G, Danz C, Somogyi AA. The influence of CYP2D6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans. Clin Pharmacol Ther. 1996;60:295\u2013307.","journal-title":"Clin Pharmacol Ther"},{"key":"81_CR14","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12458","author":"S Faruqi","year":"2014","unstructured":"Faruqi S, Wright C, Thompson R, Morice A. A randomised placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers. Br J Clin Pharmacol. 2014;. doi:10.1111\/bcp.12458 Epub ahead of print.","journal-title":"Br J Clin Pharmacol"},{"key":"81_CR15","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1096\/fj.04-1990fje","volume":"19","author":"OS Usmani","year":"2005","unstructured":"Usmani OS, Belvisi MG, Patel HJ, Crispino N, Birrell MA, Korbonits M, et al. Theobromine inhibits sensory nerve activation and cough. FASEB J. 2005;19:231\u20133.","journal-title":"FASEB J"},{"issue":"Suppl 1","key":"81_CR16","doi-asserted-by":"publisher","first-page":"S53","DOI":"10.1007\/s00408-009-9173-3","volume":"188","author":"R Eccles","year":"2010","unstructured":"Eccles R. Importance of placebo effect in cough clinical trials. Lung. 2010;188(Suppl 1):S53\u201361.","journal-title":"Lung"},{"key":"81_CR17","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.pupt.2012.03.005","volume":"25","author":"PM Wise","year":"2012","unstructured":"Wise PM, Breslin PA, Dalton P. Sweet taste and menthol increase cough reflex thresholds. Pulm Pharmacol Ther. 2012;25:236\u201341.","journal-title":"Pulm Pharmacol Ther"}],"container-title":["International Journal of Clinical Pharmacy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11096-015-0081-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11096-015-0081-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11096-015-0081-8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11096-015-0081-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T08:34:49Z","timestamp":1630571689000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11096-015-0081-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,12]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["81"],"URL":"https:\/\/doi.org\/10.1007\/s11096-015-0081-8","relation":{},"ISSN":["2210-7703","2210-7711"],"issn-type":[{"value":"2210-7703","type":"print"},{"value":"2210-7711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,12]]},"assertion":[{"value":"21 October 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}