Pharmacological characterization of a noninvasive, chronic, experimental dog model of nasal congestion.
BACKGROUND
The present experiments were undertaken to pharmacologically characterize a noninvasive, chronic, experimental dog model of nasal congestion with the overall goal of developing an effective tool for studying the mechanism of action of nasal decongestant drugs.


METHODS
Nasal patency was measured using acoustic rhinometry with chlorpheniramine and d-pseudoephedrine used as test agents. Solubilized compound 48/80 was administered as an intranasal mist to a single naris, to elicit nasal congestion in five conscious beagle dogs. Effects of localized degranulation of mast cells on nasal cavity volume, with and without pretreatment with oral decongestant drugs, were measured before and after compound 48/80 administration. Each series of experiments were repeated with a minimum 2-week rest period between trials.


RESULTS
Compound 48/80 caused a decrease of nasal cavity volume (to about 50% of control). Maximal responses were seen at 90-120 min after 48/80 administration and were of similar magnitude when trials were repeated. Oral administration of the adrenergic agonist, d-pseudoephedrine (3 mg/kg), as well as the histamine H(1) receptor antagonist, chlorpheniramine (10 mg/kg), reduced compound 48/80-induced nasal congestion with the greater effect seen with alpha-adrenoceptor blockade.


CONCLUSIONS
These results demonstrate the utility of using acoustic rhinometry to measure parameters of nasal patency in the conscious dog, and suggest that this model may provide an effective tool with which to study the actions of decongestant drugs in preclinical investigations using conscious preparations. As this technology is noninvasive, replicate determinations can be made in the same experimental subjects. Both alpha-adrenoceptor agonism and, to a lesser extent, histamine H(1) receptor antagonism appear to block compound 48/80-induced nasal congestion in this model.
Koss
Michael C
MC
Department of Cell Biology, University of Oklahoma College of Medicine, P.O. Box 26901, Oklahoma City, OK 73190, USA. michael-koss@ouhsc.edu
Yu
Yongxin
Y
Hey
John A
JA
McLeod
Robbie L
RL
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D002744:Chlorpheniramine / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D004359:Drug Therapy, Combination; D004809:Ephedrine / Q000008:administration & dosage / Q000627:therapeutic use; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D015508:Nasal Obstruction / Q000188:drug therapy / Q000503:physiopathology*; D010036:Otolaryngology / Q000379:methods*; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine; D003189:p-Methoxy-N-methylphenethylamine; D004809:Ephedrine