Differential responses to various classes of drugs in a model of allergic rhinitis in guinea pigs

Y. M A Suleimani, Ying Dong, M. J A Walker

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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-3 mg/kg, cetirizine-3 mg/kg and montelukast-10 mg/kg), L-NAME (10 or 20 mg/kg), heparin (20 mg/kg) and dexamethasone (20 mg/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 60 min 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.

Original languageEnglish
Pages (from-to)340-348
Number of pages9
JournalPulmonary Pharmacology and Therapeutics
Volume21
Issue number2
DOIs
Publication statusPublished - Apr 2008

Fingerprint

montelukast
Cetirizine
Nose
Guinea Pigs
Infiltration
Allergens
Dexamethasone
NG-Nitroarginine Methyl Ester
Pyrilamine
Heparin
Pharmaceutical Preparations
Sneezing
Pressure
Histamine Antagonists
Nasal Lavage Fluid
Autacoids
Histamine H1 Receptors
Fluids
Leukotrienes
Allergic Rhinitis

Keywords

  • Allergen challenge
  • Cetirizine
  • Dexamethasone
  • Heparin
  • Mepyramine
  • Montelukast
  • Nasal cellular infiltration

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology

Cite this

Differential responses to various classes of drugs in a model of allergic rhinitis in guinea pigs. / Suleimani, Y. M A; Dong, Ying; Walker, M. J A.

In: Pulmonary Pharmacology and Therapeutics, Vol. 21, No. 2, 04.2008, p. 340-348.

Research output: Contribution to journalArticle

@article{97346283a7d94958959e551efeaaa6ee,
title = "Differential responses to various classes of drugs in a model of allergic rhinitis in guinea pigs",
abstract = "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-3 mg/kg, cetirizine-3 mg/kg and montelukast-10 mg/kg), L-NAME (10 or 20 mg/kg), heparin (20 mg/kg) and dexamethasone (20 mg/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 60 min 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.",
keywords = "Allergen challenge, Cetirizine, Dexamethasone, Heparin, Mepyramine, Montelukast, Nasal cellular infiltration",
author = "Suleimani, {Y. M A} and Ying Dong and Walker, {M. J A}",
year = "2008",
month = "4",
doi = "10.1016/j.pupt.2007.08.004",
language = "English",
volume = "21",
pages = "340--348",
journal = "Pulmonary Pharmacology and Therapeutics",
issn = "1094-5539",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Differential responses to various classes of drugs in a model of allergic rhinitis in guinea pigs

AU - Suleimani, Y. M A

AU - Dong, Ying

AU - Walker, M. J A

PY - 2008/4

Y1 - 2008/4

N2 - 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-3 mg/kg, cetirizine-3 mg/kg and montelukast-10 mg/kg), L-NAME (10 or 20 mg/kg), heparin (20 mg/kg) and dexamethasone (20 mg/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 60 min 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.

AB - 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-3 mg/kg, cetirizine-3 mg/kg and montelukast-10 mg/kg), L-NAME (10 or 20 mg/kg), heparin (20 mg/kg) and dexamethasone (20 mg/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 60 min 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.

KW - Allergen challenge

KW - Cetirizine

KW - Dexamethasone

KW - Heparin

KW - Mepyramine

KW - Montelukast

KW - Nasal cellular infiltration

UR - http://www.scopus.com/inward/record.url?scp=39749116819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39749116819&partnerID=8YFLogxK

U2 - 10.1016/j.pupt.2007.08.004

DO - 10.1016/j.pupt.2007.08.004

M3 - Article

VL - 21

SP - 340

EP - 348

JO - Pulmonary Pharmacology and Therapeutics

JF - Pulmonary Pharmacology and Therapeutics

SN - 1094-5539

IS - 2

ER -