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; 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.[1]References
- Influence of chinoin-170, a novel antitussive, on the mucociliary activity in respiratory airways of rats, rabbits, guinea-pigs and man. Saano, V., Minker, E., Joki, S., Virta, P., Nuutinen, J., Korbonits, D. J. Pharm. Pharmacol. (1993) [Pubmed]
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