[The influence of different alpha-sympathomimetic drugs and benzalkoniumchlorid on the ciliary beat frequency of in vitro cultured human nasal mucosa cells].
BACKGROUND
An appropriate in-vitro model of the human nasal mucosa was developed, which allowed to measure the influence of different pharmaceutical substances on the ciliary beat frequency (CBF) under standardized conditions.


METHODS
The present study describes the effect of the alpha-sympathomimetic drugs naphazolin, xylometazolin and oxymetazolin as pure substances and the preservative Benzalkonium chloride in rising concentrations on the CBF. For these investigations human cells of the human nasal mucosa were cultured, which exhibited a high constancy during the equilibration measurements over at least 200 minutes.


RESULTS
The alpha-sympathomimetic drugs oxymetazoline in the concentration of 0.01% and 0.001% as well as naphazoline within all three concentrations did not show any change of the CBF. Whereas xylometazoline in the concentration of 0.1% caused a high-significant decrease of the CBF. This decrease of the CBF was however partially reversible after rinsing out. Oxymetazolin showed likewise a significant decrease of the CBF in the concentration of 0.1%. This effect however was not reversible after rinsing out with substrate-free medium, but on the contrary showed up a further decrease of CBF. The preservative benzalkonium chloride effected an irreversible ciliostatic activity already in the concentration of 0.005%.


CONCLUSIONS
From the three investigated alpha-sympathomimetic drugs only naphazoline in all measured concentrations did not show any toxic effect. With regard to its therapeutic application this drug in the concentrations 0.001%-0.1% should be preferred to all other alpha-sympathomimetic drugs. Oxymetazoline in the concentration of 0.01% and 0.001% had no toxic effect as well. It however caused an irreversible damage to the cilia in the concentration of 0.1%. This should be considered for the application of rhinological drugs especially in children. The same attention is demanded for xylometazoline, causing a high significant release of CBF in the concentration of 0.1%, which is only partially reversible. Due to the results of this study it has strongly to be advised against the use of all rhinological drugs containing the preservative benzalkonium chloride.
Mickenhagen
A
A
Jean-Uhrmacher-Institut, Universität zu Köln, Köln. axel.mickenhagen@uni-koeln.de
Siefer
O
O
Neugebauer
P
P
Stennert
E
E
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D002923:Cilia / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004867:Equipment Design; D005583:Fourier Analysis; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D008858:Microscopy, Phase-Contrast / Q000295:instrumentation; D009079:Mucociliary Clearance / Q000187:drug effects*; D009278:Naphazoline; D009297:Nasal Mucosa / Q000187:drug effects*; D010109:Oxymetazoline / Q000494:pharmacology; D012815:Signal Processing, Computer-Assisted / Q000295:instrumentation; D012984:Software; D014741:Video Recording / Q000295:instrumentation
D000316:Adrenergic alpha-Agonists; D000891:Anti-Infective Agents, Local; D001548:Benzalkonium Compounds; D007093:Imidazoles; D010109:Oxymetazoline; D009278:Naphazoline; C009695:xylometazoline