{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:28:40Z","timestamp":1787063320347,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Increased contractility of human airway smooth muscle (hASM) is a hallmark of asthma and chronic obstructive pulmonary disease (COPD). Developing new classes of bronchodilators has proved to be challenging because of efficacy and safety concerns. Quinolines hold potential therapeutic applications for the treatment of respiratory disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Relaxant effects of the novel quinoline RCD405 were investigated on contractile responses of hASM to carbachol, histamine and electrical field stimulation (EFS). The role of the non\u2010adrenergic non\u2010cholinergic (NANC) system was assessed using the inducible NO synthase inhibitor aminoguanidine and the TRPV1 agonist capsaicin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      In medium bronchi, RCD405 elicited a maximum relaxant effect (\n                      <jats:italic>E<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) of 92\u2009\u00b1\u20094% with a half\u2010maximal effective concentration (EC\n                      <jats:sub>50<\/jats:sub>\n                      ) of 45.71\u2009\u03bcM for carbachol, and an\n                      <jats:italic>E<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      of 96\u2009\u00b1\u20091% with a EC\n                      <jats:sub>50<\/jats:sub>\n                      of 12\u2009\u03bcM for histamine. In small airways, RCD405 demonstrated significant relaxant responses, with an\n                      <jats:italic>E<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      of 54\u2009\u00b1\u20097% (EC\n                      <jats:sub>50<\/jats:sub>\n                      17\u2009\u03bcM) for carbachol and 90\u2009\u00b1\u20096% (EC\n                      <jats:sub>50<\/jats:sub>\n                      20\u2009\u03bcM) for histamine. RCD405 reduced contractility in response to EFS, with\n                      <jats:italic>E<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      values of 63\u2009\u00b1\u200910% at 25\u2009Hz and 79\u2009\u00b1\u20099% at 50\u2009Hz in medium bronchi. The NANC system did not affect the bronchorelaxation induced by RCD405.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>RCD405 showed significant potential as a novel bronchodilator drug for the treatment of asthma and COPD through its ability to induce relaxation of hASM. These findings suggest that further investigation of RCD405 is warranted as a possible novel treatment of chronic respiratory disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70073","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:11:51Z","timestamp":1747721511000},"page":"4122-4133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterisation of the novel quinoline RCD405: Relaxant effects on cholinergic and histaminergic tone in human bronchi and small airways"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-5040","authenticated-orcid":false,"given":"Paola","family":"Rogliani","sequence":"first","affiliation":[{"name":"Unit of Respiratory Medicine, Department of Experimental Medicine University of Rome \u2018Tor Vergata\u2019  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-3799","authenticated-orcid":false,"given":"Clive","family":"Page","sequence":"additional","affiliation":[{"name":"Pulmonary Pharmacology Unit, Institute of Pharmaceutical Science King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Facciolo","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit IRCCS Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Lundblad","sequence":"additional","affiliation":[{"name":"R&amp;D Department, Arcede Pharma AB, Medicon Village  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-069X","authenticated-orcid":false,"given":"Luigino","family":"Calzetta","sequence":"additional","affiliation":[{"name":"Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery University of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16178"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202306-0944OC"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-024-02780-8"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2019.101814"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1980.tb07026.x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0026-4806.21.07268-2"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2015.03.007"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16272"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.124.000951"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.204644"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2025.107956"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15240"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2024.102318"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/15412555.2017.1344627"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2019.03.004"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0056OC"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.10.025"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-016-0386-8"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.4155\/ppa-2018-0030"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.004580"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201209-1739PP"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2010.09.022"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12506"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_28_1","volume-title":"StatPearls [Internet]","author":"Cuzzo B.","year":"2023"},{"key":"e_1_2_12_29_1","unstructured":"GINA. (2024).2024 GINA Main Report \u2010 Global Initiative for Asthma \u2010 GINA.https:\/\/ginasthma.org\/wp-content\/uploads\/2024\/05\/GINA-2024-Strategy-Report-24_05_22_WMS.pdf"},{"key":"e_1_2_12_30_1","unstructured":"GOLD. (2025).2025 GOLD Report \u2010 Global Initiative for Chronic Obstructive Lung Disease \u2010 GOLD.https:\/\/goldcopd.org\/wp-content\/uploads\/2024\/11\/GOLD-2025-Report-v1.0-15Nov2024_WMV.pdf"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01247-2017"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2109060"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-019-1017-y"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16900-6"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.01881.x"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb12671.x"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15054"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2016.10.009"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1846"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113220"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.04.021"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13532"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00288.2015"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S396945"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115973"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01339.x"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.119.018150"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780195171792.001.0001"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14441"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-11-9"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2013.01.002"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14909"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705905"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2007.01.004"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20071733"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2020.09.010"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T08:02:14Z","timestamp":1754294534000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,19]]},"references-count":55,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/bph.70073"],"URL":"https:\/\/doi.org\/10.1111\/bph.70073","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,19]]},"assertion":[{"value":"2025-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}