The effect of the voltage-gated sodium channel Na V 1.7 blocker PF-05089771 on cough in the guinea pig.

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 (Na _V s) lead to the rational hypothesis that subtype Na _V 1.7 is involved in initiating cough and thus may present a promising therapeutic target for antitussive therapy. We evaluated the antitussive effect of Na _V 1.7 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 Na _V 1.7 blocker PF-05089771 inhibits cough in a manner consistent with its electrophysiological effect on airway C-fibre nerve terminals.
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