Novel?7 nicotinic acetylcholine receptor modulators as potential antitussive agents

A novel series of alpha 7 nicotinic acetylcholine receptor (nAChR) modulators was designed and evaluated for an-titussive 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). alpha 7 nAChR modulators may provide a novel, non-narcotic approach to therapy in pa-tients with acute and chronic cough.