ArticleThe Journal of allergy and clinical immunology2014
Theophylline inhibits the cough reflex through a novel mechanism of action.
Article in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 36 citations in OpenAlex.
- Cough-induced severe bradycardia and syncope in a dog.The Canadian veterinary journal = La revue veterinaire canadienne · 2024Article
- Adaptive control of airway pressure during the expectoration process in a cough assist system.Frontiers in bioengineering and biotechnology · 2024Article
- Identification of the Molecular Mechanisms of Peimine in the Treatment of Cough Using Computational Target Fishing.Molecules (Basel, Switzerland) · 2020Article
- Coughing in Small Animal Patients.Frontiers in veterinary science · 2019Review
- Modelling the asthma phenotype: impact of cigarette smoke exposure.Respiratory research · 2018Article
- Synthesis and biological evaluation of the new 1,3-dimethylxanthine derivatives with thiazolidine-4-one scaffold.Chemistry Central journal · 2017Article
- Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies.American journal of respiratory and critical care medicine · 2016Article
- Pulmonary C Fibers Modulate MMP-12 Production via PAR2 and Are Involved in the Long-Term Airway Inflammation and Airway Hyperresponsiveness Induced by Respiratory Syncytial Virus Infection.Journal of virology · 2015Article
- Peripheral neural circuitry in cough.Current opinion in pharmacology · 2015Review
- Antitussive drugs--past, present, and future.Pharmacological reviews · 2014Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTheophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 80 years. In addition to bronchodilator and anti-inflammatory activity, clinical studies have suggested that theophylline acts as an antitussive agent. Cough is the most frequent reason for consultation with a family doctor, and treatment options are limited. Determining how theophylline inhibits cough might lead to the development of optimized compounds.
objectiveWe sought to investigate the inhibitory activity of theophylline on vagal sensory nerve activity and the cough reflex.
methodsUsing a range of techniques, we investigated the effect of theophylline on human and guinea pig vagal sensory nerve activity in vitro and on the cough reflex in guinea pig challenge models.
resultsTheophylline was antitussive in a guinea pig model, inhibited activation of single C-fiber afferents in vivo and depolarization of human and guinea pig vagus in vitro, and inhibited calcium influx in airway-specific neurons in vitro. A sequence of pharmacological studies on the isolated vagus and patch clamp and single-channel inside-out experiments showed that the effect of theophylline was due to an increase in the open probability of calcium-activated potassium channels. Finally, we demonstrated the antitussive activity of theophylline in a cigarette smoke exposure model that exhibited enhanced tussive responses to capsaicin.
conclusionTheophylline inhibits capsaicin-induced cough under both normal and "disease" conditions by decreasing the excitability of sensory nerves through activation of small- and intermediate-conductance calcium-activated potassium channels. These findings could lead to the development of optimized antitussive compounds with a reduced side effect potential.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.