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Interference of azelastine with anaphylaxis induced by ovalbumin challenge in actively sensitized rats.

Abstract
The inhibition of the haematological alterations and prevention of death due to systemic anaphylaxis after antigen challenge were investigated in rats after various drug treatments. The i.v. injection of ovalbumin (250 micrograms/kg) into actively sensitized rats induced marked thrombocytopenia and haemoconcentration within 5 min and significant leukocytosis within 30 min, lasting for 2 h after the challenge. Pretreatment with meclizine or terfenadine (15-30 mg/kg i.p.) inhibited antigen-induced haemoconcentration, whereas WEB 2086 (2-10 mg/kg i.p.) and PCA 4248 (5-10 mg/kg p.o.), two platelet-activating factor (PAF) antagonists, interfered with thrombocytopenia only. Azelastine (1-20 mg/kg p.o.) dose dependently inhibited antigen-induced haemoconcentration and thrombocytopenia but failed to block leukocytosis. Azelastine also inhibited the thrombocytopenia observed after the i.v. administration of PAF (4 micrograms/kg). Administration of ovalbumin at a dose of 1.5 mg/kg resulted in a lethal anaphylactic reaction in about 85% of the rats. Pretreatment with WEB 2086 (10 mg/kg i.p.), meclizine (30 mg/kg i.p.) or both increased the survival rate from 15 to 57, 68 and 87%, respectively. Azelastine alone (20 mg/kg p.o.) completely blocked the lethal reaction. It was concluded that the ability of azelastine to antagonize histamine and PAF is important for its effectiveness against anaphylactic shock.
AuthorsH C Castro-Faria-Neto, P T Bozza, A R Silva, P M Silva, M C Lima, M A Martins, R S Cordeiro, B B Vargaftig
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 213 Issue 2 Pg. 183-8 (Mar 24 1992) ISSN: 0014-2999 [Print] NETHERLANDS
PMID1355732 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Azepines
  • Dihydropyridines
  • Histamine H1 Antagonists
  • Phthalazines
  • Platelet Activating Factor
  • Triazoles
  • WEB 2086
  • PCA 4248
  • Meclizine
  • Terfenadine
  • Ovalbumin
  • azelastine
Topics
  • Anaphylaxis (prevention & control)
  • Animals
  • Azepines (pharmacology)
  • Dihydropyridines (pharmacology)
  • Dose-Response Relationship, Drug
  • Hematocrit
  • Histamine H1 Antagonists (pharmacology)
  • Leukocyte Count
  • Male
  • Meclizine (pharmacology)
  • Ovalbumin
  • Phthalazines (pharmacology)
  • Platelet Activating Factor (antagonists & inhibitors, pharmacology)
  • Platelet Count
  • Rats
  • Rats, Inbred Strains
  • Terfenadine (pharmacology)
  • Triazoles (pharmacology)

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