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ATP, an attractive target for the treatment of refractory chronic cough

Zhang, Mengru; Sykes, Dominic L.; Sadofsky, Laura R.; Morice, Alyn H.


Mengru Zhang

Dominic L. Sykes


Chronic cough is the most common complaint in respiratory clinics. Most of them have identifiable causes and some may respond to common disease-modifying therapies. However, there are many patients whose cough lacks effective aetiologically targeted treatments or remains unexplained after thorough assessments, which have been described as refractory chronic cough. Current treatments for refractory chronic cough are limited and often accompanied by intolerable side effects such as sedation. In recent years, various in-depth researches into the pathogenesis of chronic cough have led to an explosion in the development of drugs for the treatment of refractory chronic cough. There has been considerable progress in the underlying mechanisms of chronic cough targeting ATP, and ongoing or completed clinical studies have confirmed the promising antitussive efficacy of P2X3 antagonists for refractory cough. Herein, we review the foundation on which ATP target was developed as potential antitussive medications and provide an update on current clinical progresses.


Zhang, M., Sykes, D. L., Sadofsky, L. R., & Morice, A. H. (2022). ATP, an attractive target for the treatment of refractory chronic cough. Purinergic Signalling, 18, 289-305.

Journal Article Type Review
Acceptance Date Jun 8, 2022
Online Publication Date Jun 21, 2022
Publication Date 2022-09
Deposit Date Oct 19, 2022
Publicly Available Date Oct 20, 2022
Journal Purinergic Signalling
Print ISSN 1573-9538
Electronic ISSN 1573-9546
Publisher Springer
Peer Reviewed Peer Reviewed
Volume 18
Pages 289-305
Keywords Refractory chronic cough; Cough hypersensitivity; ATP; P2X3 antagonists; Gefapixant; Antitussive
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© The Author(s) 2022.
Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

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