Differential responses to various classes of drugs in a model of allergic rhinitis in guinea pigs.
Different drugs from various pharmacological classes were compared for their ability to protect against the nasal effects of acute allergen challenge in a guinea pig model. In the model, sneezing and nose rubbing were recorded after an initial allergen challenge in guinea pigs previously sensitized to egg albumin. Four days later the same guinea pigs were re-challenged a second time when anesthetised. In these anaesthetized animals, nasal airway pressure, pulmonary inflation pressure and cellular infiltration into nasal lavage fluid were measured. The drug tested were autacoid antagonists (mepyramine--3mg/kg, cetirizine--3mg/kg and montelukast--10mg/kg), L-NAME (10 or 20mg/kg), heparin (20mg/kg) and dexamethasone (20mg/kg) given either intraperitoneally or intravenously; all were given shortly before challenge. Sneezing induced by allergen challenge was statistically significantly reduced by mepyramine, cetirizine and dexamethasone whereas only cetirizine reduced nose rubbing. Changes in nasal airway pressure due to allergen exposure were reduced by cetirizine, montelukast, L-NAME, and heparin, but not by mepyramine, nor dexamethasone. In the presence of L-NAME, nasal airway pressure actually changed in the opposite direction. Cellular infiltration, as assessed by cytometry in nasal lavage fluid 60min after acute allergen challenge, was reduced by montelukast and heparin but not by antihistamines, L-NAME nor dexamethasone. This pattern of effects of the drugs, given by doses and routes previously described in the literature as being effective was not completely consistent with expected responses. The lack of effect of dexamethasone probably reflects the fact that it was given acutely whereas in the clinic chronic administration is used. The two antihistamines were not identical in their actions, presumably reflecting the fact that cetirizine has therapeutic actions not entirely confined to blockade of H1 receptors. Montelukast has not been reported to have major effects on sneezing and itching in the clinic but reduces nasal obstruction (lower nasal airway pressure or nasal patency). Montelukast's effects on cellular infiltration indicate the possible involvement of leukotrienes. Heparin has actions on inflammatory cell infiltration. This could explain its profile of reducing both cellular infiltration, and increased nasal airway pressure.
Al Suleimani
Yousuf M
YM
Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Oman. rsdaa@interchange.ubc.ca
Dong
Ying
Y
Walker
Michael J A
MJ
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use; D000208:Acute Disease; D000818:Animals; D017332:Cetirizine / Q000008:administration & dosage / Q000627:therapeutic use; D003521:Cyclopropanes; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000627:therapeutic use; D015508:Nasal Obstruction / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011738:Pyrilamine / Q000008:administration & dosage / Q000627:therapeutic use; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D012912:Sneezing / Q000187:drug effects / Q000276:immunology; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D006634:Histamine H1 Antagonists; D011804:Quinolines; D013440:Sulfides; D003907:Dexamethasone; D006493:Heparin; D010047:Ovalbumin; D011738:Pyrilamine; C093875:montelukast; D019331:NG-Nitroarginine Methyl Ester; D017332:Cetirizine