Pharmacology of Antihistamines

This article reviews the molecular biology of the interaction of histamine with its H(1)-receptor and describes the concept that H(1)-antihistamines are not receptor antagonists but are inverse agonists i.e. they produce the opposite effect on the receptor to histamine. It then discourages the use of first-generation H(1)-antihistamines in clinical practice today for two main reasons. First, they are less effective than second generation H(1)-antihistamines. Second, they have unwanted side effects, particularly central nervous system and anti-cholinergic effects, and have the potential for causing severe toxic reactions which are not shared by second-generation H(1)-antihistamines. There are many efficacious and safe second-generation H(1)-antihistamines on the market for the treatment of allergic disease. Of the three drugs highlighted in this review, levocetirizine and fexofenadine are the most efficacious in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals while fexofenadine has a relatively short duration of action requiring twice daily administration for full all round daily protection. While desloratadine is less efficacious, it has the advantages of rarely causing somnolence and having a long duration of action. Lastly, all H(1)-antihistamines have anti-inflammatory effects but it requires regular daily dosing rather than dosing 'on-demand' for this effect to be clinically demonstrable.