The effect of histamine-H1 receptor antagonism with terfenadine on concentration-related AMP-induced bronchoconstriction in asthma.
Selective histamine-H1 receptor antagonists inhibit adenosine 5'-monophosphate (AMP)-induced bronchoconstriction by greater than 80% when expressed as a percentage inhibition of the FEV1 time-response curve following inhalation of the provocation concentration of AMP required to produce a 20% decrease in FEV1 from baseline (PC20). To investigate this further we have determined that, in eight mild atopic asthmatic subjects, terfenadine (180 mg), administered 3 hr pre-challenge, increases the geometric mean PC20 for histamine from 0.4 (range 0.03-3) mg/ml after placebo, to 20.2 (range 0.6-64) mg/ml following active treatment (P less than 0.0001). For AMP, the PC20 increased from 9.3 (range 1.0-113.3) mg/ml after placebo, to 150.2 (range 32.1-1177.7) mg/ml with terfenadine (P less than 0.0001). This 16.2-fold (range, 5.5-47.9) displacement to the right of the AMP concentration-response curve by a selective histamine-H1 receptor antagonist emphasizes the central role of histamine in the airways response to this nucleotide.
Phillips
G D
GD
Immunopharmacology Group, Southampton General Hospital, U.K.
Polosa
R
R
Holgate
S T
ST
D000328:Adult; D001249:Asthma / Q000276:immunology*; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001986:Bronchial Spasm / Q000139:chemically induced / Q000276:immunology*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000276:immunology; D011897:Random Allocation; D011969:Receptors, Histamine H1 / Q000187:drug effects* / Q000276:immunology; D016593:Terfenadine
D001559:Benzhydryl Compounds; D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D016593:Terfenadine; D000242:Cyclic AMP