Document Detail


Synergistic antiallergic activity of combined histamine H1- and cysteinyl leukotriene1-receptor blockade in human bronchus.
MedLine Citation:
PMID:  11432448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mast cell histamine (HA) and cysteinyl leukotrienes (CysLT) account for most of the early phase bronchospasm in asthma. However, activation of the smooth muscle CysLT1-receptor plays a major role in asthmatic bronchospasms. CysLT-receptor antagonists or CysLT-synthesis inhibitors are efficacious in asthma but do not completely abolish asthmatic bronchospasms. A recent clinical study showed that combined antagonists loratadine (H1) and zafirlukast (CysLT1) were more effective against allergic bronchospasms than either drug alone. We examined the combined efficacy of H1- and CysLT1-receptor antagonists in allergic human bronchus. The H1- and CysLT1-receptor antagonists chlorpheniramine (CTM; 1 microM) and MK-571 (0.03 microM), were tested alone and in combination, against anti-human IgE antibody (Ab)-induced contractions of passively sensitized isolated human bronchus. Ab-induced allergic contractions were reduced 15% and 36% by CTM (1 microM) and MK-571 (0.03 microM), respectively. Combined CTM (1 microM) and MK-571 (0.03 microM) significantly inhibited the Ab response by 87%. Mechanistic investigations in isolated human bronchus and cultured human cord blood mast cells suggest that H1- and CysLT-receptor interactions likely occur at the airway smooth muscle level. CTM and MK-571 synergistically inhibited human allergic bronchospasm in the present in vitro model. The mechanism underlying this synergistic activity requires further investigation.
Authors:
L M Ruck; C A Rizzo; J C Anthes; S Eckel; R W Egan; F M Cuss; J A Hey
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  68     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-07-02     Completed Date:  2001-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2825-34     Citation Subset:  IM    
Affiliation:
Allergy, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. lori.ruck@spcorp.com
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MeSH Terms
Descriptor/Qualifier:
Adult
Bronchi / drug effects*,  immunology
Bronchial Spasm / immunology,  prevention & control
Cells, Cultured
Dose-Response Relationship, Drug
Drug Synergism
Female
Histamine / pharmacology
Histamine H1 Antagonists / pharmacology*
Humans
Immunization, Passive
Immunoglobulin E / immunology
Leukotriene Antagonists* / pharmacology*
Leukotriene D4 / pharmacology
Male
Mast Cells / drug effects
Membrane Proteins*
Middle Aged
Muscle Contraction / drug effects,  immunology
Muscle, Smooth / drug effects,  immunology
Propionates / pharmacology
Quinolines / pharmacology
Receptors, Leukotriene*
Chemical
Reg. No./Substance:
0/Histamine H1 Antagonists; 0/Leukotriene Antagonists; 0/Membrane Proteins; 0/Propionates; 0/Quinolines; 0/Receptors, Leukotriene; 0/cysteinyl leukotriene receptor 2; 0/leukotriene D4 receptor; 115104-28-4/verlukast; 37341-29-0/Immunoglobulin E; 51-45-6/Histamine; 73836-78-9/Leukotriene D4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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