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.
Saano
V
V
Department of Pharmacology, A.I. Virtanen Institute, University of Kuopio, Finland.
Minker
E
E
Joki
S
S
Virta
P
P
Nuutinen
J
J
Korbonits
D
D
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D002923:Cilia / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D010069:Oxadiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D000996:Antitussive Agents; D010069:Oxadiazoles; C065538:CHINOIN 170; D013806:Theophylline