Evolution of H1-receptor antagonist treatment

Abstract

The introduction of relatively nonsedating H1-receptor antagonists ushered in a new era in the symptomatic treatment of allergic disorders. Unlike first-generation H1-receptor antagonists, the second-generation compounds (such as astemizole, cetirizine, loratadine, and terfenadine) do not cross the blood-brain barrier readily and are thus comparatively free of central nervous system effects. The pharmacokinetic and pharmacodynamic profiles vary considerably by agent, but most of the second-generation drugs are suitable for once-daily dosing. Efficacy of the H1 antagonists is maintained during chronic therapy. The second-generation H1-receptor antagonists are appropriate for use as first-line treatment of allergic rhinoconjunctivitis and urticaria. These agents also have a modest, direct beneficial effect in patients with chronic asthma. The role of the newer H1-receptor antagonists in the treatment of atopic dermatitis, upper respiratory tract infections, and otitis media remains undefined. Recently, the gene encoding the histamine H1 receptor was cloned from bovine adrenal medullae. Emerging evidence suggests that more than one subtype of H1 receptor may exist. It is hoped these advances will pave the way for further improvements in H1-antagonist therapy.