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

• Published in: Journal of pharmacy and pharmacology Vol. 45; no. 9; p. 799
• Main Authors: Saano, V, Minker, E, Joki, S, Virta, P, Nuutinen, J, Korbonits, D
• Format: Journal Article
• Language: English
• Published: England 01.09.1993
• Subjects: Animals; Antitussive Agents - pharmacology; Cilia - drug effects; Cilia - physiology; Dose-Response Relationship, Drug; Female; Guinea Pigs; Humans; In Vitro Techniques; Injections, Intravenous; Male; Mucociliary Clearance - drug effects; Oxadiazoles - administration & dosage; Oxadiazoles - pharmacology; Rabbits; Rats; Rats, Wistar; Theophylline - administration & dosage; Theophylline - analogs & derivatives; Theophylline - pharmacology; Trachea - drug effects; Trachea - physiology
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.1993.tb05688.x

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.