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.