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.
T10 T11 T12 T13 T14 T15 T16 T17 T1 T2 T3 T4 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
histamine histamine histamine terfenadine AMP histamine-H1 receptor histamine-H1 receptor histamine-H1 receptor histamine AMP terfenadine histamine adenosine 5'-monophosphate AMP terfenadine AMP AMP