EVOLUTION OF H-1-RECEPTOR ANTAGONIST TREATMENT

The introduction of relatively nonsedating H-1-receptor antagonists ushered in a new era in the symptomatic treatment of allergic disorders. Unlike first-generation H-1-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 H-1 antagonists is maintained during chronic therapy. The second-generation H-1-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 H-1-receptor antagonists in the treatment of atopic dermatitis, upper respiratory tract infections, and otitis media remains undefined. Recently, the gene encoding the histamine H-1 receptor was cloned from bovine adrenal medullae. Emerging evidence suggests that more than one subtype of H-1 receptor may exist. It is hoped these advances will pave the way for further improvements in H-1-antagonist therapy.