Mucolytic and antitussive effects of erdosteine.
To investigate the influence of erdosteine, a new homocysteine-derived expectorant, on airway clearance we studied the effects of the drug on the viscosity of mucin, on the mucociliary transport rate in quails, on airway secretion in rats and on the cough reflex in guinea-pigs. The active metabolite of erdosteine, M1 (10 microM to 1 mM), significantly reduced the viscosity of porcine stomach mucin. Erdosteine by itself did not reduce viscosity. Erdosteine significantly promoted mucociliary transport in quails and increased airway secretion in rats. The effect was still apparent 24h after administration. Erdosteine significantly suppressed citric acid-induced cough reflexes in guinea-pigs but did not suppress mechanical stimuli-induced cough reflexes. Erdosteine suppressed the reduction of the recovery volume of bronchoalveolar lavage fluid and albumin leakage into the fluid in citric acid-exposed guinea-pigs. These results indicate that erdosteine removes sputum by reducing its viscosity, and by promoting mucociliary transport and sustained enhancement of airway secretion. It also suppressed the chemical stimulation-induced cough reflex and plasma leakage into the airway. These results suggest that erdosteine is an excellent expectorant with several modes of action.
Hosoe
H
H
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Company Limited, Shizuoka, Japan.
Kaise
T
T
Ohmori
K
K
Isohama
Y
Y
Kai
H
H
Takahama
K
K
Miyata
T
T
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D019343:Citric Acid / Q000009:adverse effects; D003371:Cough / Q000209:etiology; D004347:Drug Interactions; D005100:Expectorants / Q000494:pharmacology; D005260:Female; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D009093:Mucus / Q000378:metabolism*; D010812:Physical Stimulation; D011784:Quail; D051381:Rats; D013268:Stimulation, Chemical; D013552:Swine; D013864:Thioglycolates / Q000378:metabolism / Q000494:pharmacology*; D013876:Thiophenes / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014783:Viscosity / Q000187:drug effects*
D000996:Antitussive Agents; D005100:Expectorants; D013864:Thioglycolates; D013876:Thiophenes; D019343:Citric Acid; C048498:erdosteine