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Clinical & Experimental Allergy

The effect of histamine-H1 receptor antagonism with terfenadine on concentration-related AMP-induced bronchoconstriction in asthma

Authors


Dr G. D. Phillips, Immunopharmacology Group, Medicine 1, Level D, Centre Block, Southampton General Hospital, Tremona Road, Southampton SO9 4XY, U.K.

Summary

Selective histamine-H1 receptor antagonists inhibit adenosine 5′-monophosphate (AMP)-induced bronchoconstriction by > 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<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<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.

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