INFLUENCE OF CHINOIN-170, A NOVEL ANTITUSSIVE, ON THE MUCOCILIARY ACTIVITY IN RESPIRATORY AIRWAYS OF RATS, RABBITS, GUINEA-PIGS AND MAN

Chinoin-170 (Ch-170: l-1.2,4-oxadiazol-3-yl)methyl]1H-purine-2,6-dione ) is a new antitussive with bronchodilating activity. Its effects on t he ciliary beating frequency (CBF) and mucociliary clearance were stud ied. In tracheal explants of rats, Ch-170 dose-dependently at concentr ations 2 and 5 mg mL-1 depressed CBF by 24 and 33%, respectively. In h uman mucosal explants, however, no effects were seen at concentrations up to 5 mg mL-1. In anaesthetized guinea-pigs, an intravenous 50 mg k g-1 dose of Ch-170 caused no changes, and 100 mg kg-1 increased the CB F by 15%. Intravenous Ch-170 dose-dependently increased by 93 (50 mg k g-1), 179 (70 mg kg-1) and 253%. (100 mg kg-1) the tracheobronchial mu cociliary clearance in rabbits. The effect, studied using Tc-99m-label led red blood cells as a marker. was of similar quantity to that broug ht about by administering 16, 25 and 40 mg kg-1 doses of bromhexine. I t is concluded that unlike many older antitussives. Ch-170 in-vitro on ly slightly decreases the CBF in rats and has no adverse effects on th e 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 i ncrease is most probably a result of changes in the production and the properties of respiratory mucus.