American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2021
Randomized Controlled TrialAprepitant For Cough in Lung Cancer: A Randomised Placebo-Controlled Trial and Mechanistic Insights.
Rationale: Effective cough treatments are a significant unmet need in patients with lung cancer. Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of NK-1 (neurokinin 1) receptors, a mechanism also implicated in cough. Objectives: To assess aprepitant in patients with lung cancer with cough and evaluate mechanisms in vagal nerve tissue. ⋯ Substance P depolarized both guinea pig and human vagus nerve. Aprepitant significantly inhibited substance P-induced depolarization by 78% in guinea pig (P = 0.0145) and 94% in human vagus (P = 0.0145). Conclusions: Substance P activation of NK-1 receptors appears to be an important mechanism driving cough in lung cancer, and NK-1 antagonists show promise as antitussive therapies.
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Am. J. Respir. Crit. Care Med. · Mar 2021
Editorial CommentNeurokinin-1 Receptor Inhibition and Cough.