Molecular pharmacology of second-generation antihistamines

Histamine was the first allergic mediator identified in the early part of t his century. it has three defined receptors, but most effects of histamine in allergic reactions are through the HI receptor The first HI antagonists were introduced into clinical use in the late 1940s, and drugs of this clas s are still the preferred initial choice for management of allergic rhiniti s and uuricnrin. The first-generation drugs were characterized by nonspecif ic binding to many receptors and penetration of the blood-brain barrier res ulting in multiple sine effects. Within the central nervous system (CNS), i nterference with normal histamine binding to the HI receptor is associated with drowsiness and psychomotor impairment. The second-generation drugs hav e a much improved benefit/adverse effect profile, largely based on greater potency, receptor specificity and lower CNS penetration The potency of anti histamines for blocking HI receptors can be compared by their inhibition of the cutaneous wheal and flare response to histamine. These drugs seem to h ave additional antiallergic properties related to blockade of mediator rele ase and interference with cellular recruitment and activation. Clinical tri als comparing the efficacy of antihistamines in rhinitis and asthma are rev iewed Recent studies have explored the potential of antihistamines to preve nt the progression of allergy and their enhanced efficacy when combined wit h leukotriene antagonists.