Effects of a specific cysteinyl leukotriene antagonist, pranlukast, on antigen-induced cysteinyl leukotriene-mediated rhinitis in guinea pigs.

Abstract

To examine the effects of a specific cysteinyl leukotriene (cysLT) antagonist, pranlukast, on allergic rhinitis, antigen-induced rhinitis in guinea pigs was modified by pretreatment with an cyclooxygenase inhibitor (indomethacin) followed by an H1-blocker (pyrilamine). Intranasal ovalbumin (OVA) administration in actively sensitized guinea pigs resulted in concentration-dependent increases in nasal permeability and nasal airway resistance (NAR). Although pyrilamine (1 mg/kg, i.v.) abolished these antigen-induced changes, pretreatment with indomethacin (5 mg/kg, i.v.) followed by pyrilamine enhanced these responses to a degree similar to that observed with OVA challenge alone. Analyses of nasal perfusate in indomethacin/pyrilamine-pretreated animals showed that cysLTs increased by 270.8%, whereas thromboxane B2 decreased by 88.3% as compared with those on challenged with OVA alone. Oral administration of pranlukast (1-10 mg/kg) dose-dependently prevented increases in nasal permeability and NAR of indomethacin/pyrilamine-pretreated animals. However, an anti-allergic agent, azelastine, did not affect these responses. These results indicate that pranlukast suppresses antigen-induced cysLT-mediated responses of allergic rhinitis in actively sensitized guinea pigs. A cysLT antagonist, pranlukast, may thus prevent cysLT-mediated symptoms of allergic rhinitis.

• Authors: M Fujita, Y Yonetomi, H Takeda, N Nakagawa, K Kawabata, H Ohno
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 75 Issue 4 Pg. 347-53 (Dec 1997) ISSN: 0021-5198 [Print] Japan
• PMID: 9469640 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Allergic Agents
• Anti-Asthmatic Agents
• Chromones
• Cyclooxygenase Inhibitors
• Histamine H1 Antagonists
• Leukotriene Antagonists
• Phthalazines
• SRS-A
• Thromboxane B2
• Ovalbumin
• Pyrilamine
• pranlukast
• Indomethacin
• azelastine

Topics

• Airway Resistance (drug effects)
• Animals
• Anti-Allergic Agents (pharmacology)
• Anti-Asthmatic Agents (administration & dosage, pharmacology)
• Chromones (administration & dosage, pharmacology)
• Cyclooxygenase Inhibitors (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Guinea Pigs
• Histamine H1 Antagonists (pharmacology)
• Indomethacin (pharmacology)
• Leukotriene Antagonists
• Nasal Mucosa (drug effects, metabolism)
• Ovalbumin
• Phthalazines (pharmacology)
• Pyrilamine (pharmacology)
• Rhinitis, Allergic, Perennial (chemically induced, drug therapy)
• SRS-A (antagonists & inhibitors)
• Thromboxane B2 (metabolism)