Novel α7 nicotinic acetylcholine receptor modulators as potential antitussive agents

A novel series of α7 nicotinic acetylcholine receptor (nAChR) modulators was designed and evaluated for antitussive activity in an in vivo guinea pig model of chemically induced cough. Compound 16 at all tested doses (9.5, 3 and 1 mg/kg) significantly (p < 0.01) reduced the cumulative number of coughs and showed similar results to a positive control (codeine at 30 mg/kg). Among three different administration routes (intraperitoneal, oral and inhalation), compound 16 exerted a significant antitussive effect in guinea pigs at an inhaled dose as low as 0.4 mg/kg (p < 0.05). α7 nAChR modulators may provide a novel, non-narcotic approach to therapy in patients with acute and chronic cough.