Effect of azelastine on platelet-activating factor and antigen-induced pleurisy in rats.

Abstract

The interference of azelastine with pleurisy induced by antigen was investigated in actively sensitized rats. The antigenic challenge (ovalbumin, 12 micrograms/cavity) caused early plasma leakage, which peaked within 4 h, accompanied by intense neutrophil infiltration. Pleural exudate decayed 24 h after antigen provocation, when a long-lasting increase in the number of resident eosinophils was observed. Oral pretreatment with azelastine (1-10 mg/kg) dose dependently inhibited the vasopermeation (ED50 = 4.2 mg/kg) and reduced the pleural exudate (ED50 = 6.8 mg/kg) induced by the antigen. In contrast, azelastine (10 mg/kg) failed to modify the neutrophil influx observed at 4 h and the eosinophil accumulation detected at 24 h. Azelastine was also effective against rat pleurisy induced by either platelet-activating factor (PAF-acether), histamine or serotonin. It reduced exudation and the increase in the number of mononuclear cells, neutrophils and eosinophils observed 6 h after PAF-acether. Nevertheless, antagonism of PAF-acether may not be relevant to the inhibition observed in the present model of allergic pleurisy, as the inhibition was refractory to three distinct PAF-acether receptor antagonists. In contrast, like azelastine, the histamine H1 receptor antagonist meclizine and the dual histamine and serotonin receptor antagonist cyproheptadine blocked antigen-induced exudation and failed to interfere with cell influx. We conclude that the anti-exudatory activity of oral azelastine on antigen-induced pleurisy is consistent with it exerting direct effects against vasoactive amines, but is not related to an effect against leucocyte infiltration nor to its ability to inhibit PAF-acether.

• Authors: M C Lima, M A Martins, S A Perez, P M Silva, R S Cordeiro, B B Vargaftig
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 197 Issue 2-3 Pg. 201-7 (May 17 1991) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1680710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens
• Histamine H1 Antagonists
• Phthalazines
• Platelet Activating Factor
• Serotonin
• Histamine
• Ovalbumin
• azelastine

Topics

• Animals
• Antigens (administration & dosage)
• Female
• Histamine (pharmacology)
• Histamine H1 Antagonists (pharmacology)
• Leukocytes (drug effects, pathology)
• Male
• Ovalbumin (immunology)
• Phthalazines (pharmacology)
• Platelet Activating Factor (antagonists & inhibitors, pharmacology)
• Pleural Effusion (etiology, pathology, prevention & control)
• Pleurisy (etiology, pathology, prevention & control)
• Rats
• Rats, Inbred Strains
• Serotonin (pharmacology)