The effect of the voltage-gated sodium channel NaV1.7 blocker PF-05089771 on cough in the guinea pig.

Abstract

Cough in chronic respiratory diseases is a common symptom associated with significant comorbidities including visceral pain. Available antitussive therapy still has limited efficacy. Recent advances in the understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that subtype NaV1.7 is involved in initiating cough and thus may present a promising therapeutic target for antitussive therapy. We evaluated the antitussive effect of NaV1.7 blocker PF-05089771 administered systemically and topically in awake guinea pigs using capsaicin cough challenge. Compared to vehicle, peroral or inhaled PF-05089771 administration caused about 50-60 % inhibition of cough at the doses that did not alter respiratory rate. We conclude that the NaV1.7 blocker PF-05089771 inhibits cough in a manner consistent with its electrophysiological effect on airway C-fibre nerve terminals.

• Authors: Mariana Brozmanova, Tomas Buday, Milena Konarska, Jana Plevkova
• Journal: Respiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 299 Pg. 103856 (05 2022) ISSN: 1878-1519 [Electronic] Netherlands
• PMID: 35114369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Antitussive Agents
• PF-05089771
• Phenyl Ethers
• Sulfonamides
• Voltage-Gated Sodium Channel Blockers
• Voltage-Gated Sodium Channels

Topics

• Animals
• Antitussive Agents (pharmacology, therapeutic use)
• Cough (drug therapy)
• Guinea Pigs
• Phenyl Ethers
• Sulfonamides
• Voltage-Gated Sodium Channel Blockers (pharmacology, therapeutic use)
• Voltage-Gated Sodium Channels (physiology)