Influence of combined voltage-gated sodium channel NaV1.7 and NaV1.8 inhibitors on cough in a guinea pig model.

Abstract

Pathological excessive cough is a serious clinical problem in many patients. It is no doubt that an increased activation and sensitization of airway vagal C-fibres in disease stems from dysregulation of the neural pathways that control cough. Due to the limited efficacy and unwanted side effects of current antitussives, there is a continual demand for the development of a novel more effective antitussive. Since voltage-gated sodium channels (NaVs) are absolutely required for action potentials initiation and conduction irrespective of the stimulus, NaVs became a promising and attractive neural target. Current studies establish that NaV1.7 and NaV1.8 inhibitors have the potential to suppress cough. In this study, we demonstrated that inhaled aerosol of NaV1.7 inhibitor PF-05089771 (10 μM) and NaV1.8 inhibitor A-803467 (1 mM) mixture inhibited the capsaicin-induced cough by ≈ 60 % and citric acid-induced cough by ≈ 65 % at doses that did not modify respiratory rate. Our previous and present studies indicate that NaV1.7 and NaV1.8 may present promising therapeutic targets for antitussive therapy.

• Authors: Mariana Brozmanova, Tomas Buday, Janka Jakusova, Jana Melegova, Jana Plevkova
• Journal: Respiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 312 Pg. 104043 (06 2023) ISSN: 1878-1519 [Electronic] Netherlands
• PMID: 36871863 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Antitussive Agents
• Voltage-Gated Sodium Channels
• Sodium Channel Blockers

Topics

• Guinea Pigs
• Animals
• Cough (chemically induced, drug therapy, metabolism)
• Antitussive Agents (therapeutic use)
• Voltage-Gated Sodium Channels (metabolism)
• Vagus Nerve (physiology)
• Sodium Channel Blockers (adverse effects)