Emil Minker

Influence of Chinoin-170, a novel antitussive, on the mucociliary activity in respiratory airways of rats, rabbits, guinea-pigs and man

Abstract— Chinoin‐170 (Ch‐170; 3,7‐dihydro‐1,3‐dimethyl‐7‐[(5‐methyl‐1,2,4‐oxadiazol‐3‐yl)methyl]1H‐purine‐2,6‐dione) is a new antitussive with bronchodilating activity. Its effects on the ciliary beating frequency (CBF) and mucociliary clearance were studied. In tracheal explants of rats, Ch‐170 dose‐dependently at concentrations 2 and 5 mg mL−1 depressed CBF by 24 and 33%, respectively. In human mucosal explants, however, no effects were seen at concentrations up to 5 mg mL−1. In anaesthetized guinea‐pigs, an intravenous 50 mg kg−1 dose of Ch‐170 caused no changes, and 100 mg kg−1 increased the CBF by 15%. Intravenous Ch‐170 dose‐dependently increased by 93 (50 mg kg−1), 179 (70 mg kg−1) and 253% (100 mg kg−1) the tracheobronchial mucociliary clearance in rabbits. The effect, studied using 99mTc‐labelled red blood cells as a marker, was of similar quantity to that brought about by administering 16, 25 and 40 mg kg−1 doses of bromhexine. It is concluded that unlike many older antitussives, Ch‐170 in‐vitro only slightly decreases the CBF in rats and has no adverse effects on the CBF in human mucosal explants at concentrations up to 5 mg mL−1. In‐vivo, Ch‐170 does not significantly alter the CBF in guinea‐pigs, but dose‐dependently increases the mucociliary clearance in rabbits. The increase is most probably a result of changes in the production and the properties of respiratory mucus.