title: Combined Inhibition of Histamine H1 Receptors and Leukotrienes Reduces Compound 48/80-Induced Contraction of the Human Bronchus in vitro.
abstract: OBJECTIVE
  Bronchial asthma continues to be a big challenge to therapy. Mast cells play an important role in allergic asthma. Histamine and leukotrienes are established mast cell mediators, but antihistamines currently play no role in asthma therapy.
  
  
  METHODS
  Human bronchial strips were exposed to the mast cell activator compound 48/80 (200 μg/ml) in isolated organ experiments.
  
  
  RESULTS
  The contractile response was not inhibited by the H1 receptor antagonist antihistamine chloropyramine (0.3 μmol/l), the leukotriene cys-LT1 receptor antagonist MK 571 (3 μmol/l), the 5-lipoxygenase inhibitor MK 886 (5 μmol/l), the cyclo-oxygenase inhibitor indomethacin (5 μmol/l), tetrodotoxin, or atropine. Chloropyramine, combined with either MK 571 or MK 886 significantly reduced the response.
  
  
  CONCLUSIONS
  A supra-additive effect is proposed for the antihistamine and the anti-leukotrienes, which might have relevance to human asthma therapy as well; such a combination deserves a large-scale clinical study. These data also indicate that substances like compound 48/80 should be denoted as mast cell activators rather than 'histamine liberators'.
authors.affiliation: Departments of Pharmacology and Pharmacotherapy, University Medical School of Px00E9;cs Clinical Centre, Px00E9;cs, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Benko
authors.forename: Tamas F
authors.initials: TF
authors.lastname: Molnar
authors.forename: Veronika
authors.initials: V
authors.lastname: Szombati
authors.forename: István
authors.initials: I
authors.lastname: Benkö
authors.forename: Lorand
authors.initials: L
authors.lastname: Bartho
mesh_terms: D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004357:Drug Synergism; D005029:Ethylenediamines / Q000008:administration & dosage / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007551:Isotonic Contraction / Q000187:drug effects*; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D018077:Receptors, Leukotriene / Q000378:metabolism*; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000494:pharmacology; D002722:Chlorobenzenes
chemical_list: D005029:Ethylenediamines; D006634:Histamine H1 Antagonists; D007211:Indoles; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D011422:Propionates; D011804:Quinolines; D011969:Receptors, Histamine H1; D018077:Receptors, Leukotriene; D003189:p-Methoxy-N-methylphenethylamine; C060893:MK-886; D002722:Chlorobenzenes; C004664:chloropyramine; C059141:verlukast