A comparison of a new mucolytic N-acetylcysteine L-lysinate with N-acetylcysteine: airway epithelial function and mucus changes in dog.
A newly synthesized mucolytic agent, N-acetylcysteine L-lysinate (Nacystelyn) was studied. Tracheal mucus velocity (TMV), transepithelial potential difference (PD), rheological properties, and ion content of collected airway secretions were evaluated in six healthy mongrel dogs after placebo, Nacystelyn (NAL) and acetylcysteine (NAC) metered dose inhaler (MDI) aerosols. Although TMV was increased and viscoelasticity decreased after both treatments, the treatment effect with NAL was significantly greater. Furthermore, NAL increased the negative PD and CI- content of secretions in the trachea, an effect not observed after NAC. Both compounds increased ciliary beat frequency (CBF) on the frog palate at a concentration range similar to that approximated in dog airways. The increased mucociliary clearance could be partially explained by favourable rheological changes combined with stimulation of CBF. Since both compounds break disulfide bonds in mucus polymers, the greater change in mucus rheology and clearance rate after NAL, without change in water content, could be explained by the increase in CI- content. Nacystelyn appears to combine different modes of action which synergistically cause an increase in the clearance rate of airway secretions.
Tomkiewicz
R P
RP
Pulmonary Research Group, University of Alberta, Edmonton, Canada.
App
E M
EM
De Sanctis
G T
GT
Coffiner
M
M
Maes
P
P
Rubin
B K
BK
King
M
M
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D004285:Dogs; D005100:Expectorants / Q000494:pharmacology*; D005260:Female; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D009093:Mucus / Q000378:metabolism / Q000502:physiology; D014132:Trachea / Q000187:drug effects; D014783:Viscosity / Q000187:drug effects
D005100:Expectorants; C086501:N-acetylcysteine lysinate; D008239:Lysine; D000111:Acetylcysteine