A COMPARISON OF THE ACTIONS OF H-1 AND H-2 ANTIHISTAMINES ON HISTAMINE-INDUCED BRONCHOCONSTRICTION AND CUTANEOUS WHEAL RESPONSE IN ASTHMATIC-PATIENTS

[摘要] The effect of an H1 antihistamine, an H2 antihistamine, and the combination of the 2 drugs on both histamine-induced bronchoconstriction and dermal whealing was examined in 5 patients with mild asthma. Chlorpheniramine (8 mg), cimetidine (300 mg), the combination of both and placebo were administered orally to each patient for a single dose and for 7 consecutive doses given every 6 h after a double-blind, randomized protocol. The airway response to inhaled histamine and the wheal size induced by the intradermal injection of histamine were determined in every patient 2 h after the final drug dose. A single dose of chlorpheniramine produces a significant increase in the threshold of histamine-induced bronchoconstriction as measured by the provocative histamine dose producing 20% decrease in 1-s forced expiratory volume (PD20-FEV1), and this effect was significantly enhanced after 7 doses. Cimetidine caused a significant decrease in the threshold of histamine-induced bronchoconstriction, but this was not augmented by 7 doses. Only chlorpheniramine, when given for 7 doses, improved the baseline FEV1 and forced expiratory flow during the middle half of forced vital capacity (FEF25%-75%). Chlorpheniramine in both single and multiple doses and the combination of chlorpheniramine and cimetidine given for 7 doses produced a significant inhibition of histamine-induced dermal wheals, but cimetidine alone had no effect. H1 and H2 receptors are present in the airways of asthmatic patients and they mediate opposite effects. A cumulative effect was demonstrated with the repeated administration of chlorpheniramine but not with cimetidine. The role of H1 and H2 receptors differs in the bronchi from that seen in the dermal vessels of asthmatic patients and are in contrast to those of normals. The H2 receptor effect on histamine-induced skin wheals appears deficient, further supporting earlier suggestions of the presence of an H2 receptor defect in asthmatic patients.