P2X3-Receptor Antagonists as Potential Antitussives: Summary of Current Clinical Trials in Chronic Cough

Cough is among the most common complaints for which patients worldwide seek medical attention. In a majority of patients with chronic cough (defined as cough of greater than 8 weeks’ duration), successful management results from a thorough evaluation and treatment of underlying causes. In a subgroup...

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Bibliographic Details
Published in:Lung 2020-08, Vol.198 (4), p.609-616
Main Authors: Dicpinigaitis, Peter V., McGarvey, Lorcan P., Canning, Brendan J.
Format: Article
Language:English
Subjects:
Clinical trials
Cough
Drug development
Health aspects
Medical colleges
Medicine
Medicine & Public Health
Patients
Pharmaceutical industry
Physical instruments
Pneumology/Respiratory System
Purine P2X receptors
Receptors
Respiratory agents
Side effects
State of the Art Review
Subgroups
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Summary:Cough is among the most common complaints for which patients worldwide seek medical attention. In a majority of patients with chronic cough (defined as cough of greater than 8 weeks’ duration), successful management results from a thorough evaluation and treatment of underlying causes. In a subgroup of patients, however, cough proves refractory to therapeutic trials aimed at known reversible causes of chronic cough. Such patients are appropriately termed as having refractory chronic cough. At present, safe and effective medications are lacking for this challenging patient population. Currently available therapeutic options are usually ineffective or achieve antitussive effect at the expense of intolerable side effects, typically sedation. Fortunately, the past decade has witnessed great progress in elucidating underlying mechanisms of cough. From that knowledge, aided by the development of validated instruments to measure objective and subjective cough-related end points, numerous antitussive drug development programs have emerged. The most active area of inquiry at present involves antagonists of the purinergic P2X receptors. Indeed, four clinical programs (one in Phase 3 and three in Phase 2) are currently underway investigating antagonists of receptors comprised entirely or partially of the P2X3 subunit as potential antitussive medications. Herein we review the foundation on which P2X receptor antagonists were developed as potential antitussive medications and provide an update on current clinical trials.
ISSN:0341-2040
1432-1750
DOI:10.1007/s00408-020-00377-8