As their names imply, first generation antihistamines have been around longer than the second generation antihistamines. There is also a third generation antihistamine class. The main difference between them is the first generation antihistamines tend to cause more drowsiness, dry mouth, and dry eyes compared to the second and third generation antihistamines.

First generation antihistamines include chlorpheniramine (Chlor-Tripolon®), diphenhydramine (Benadryl® and various generics), and triprolidine (Actifed® - includes a decongestant). Second generation antihistamines include cetirizine (Reactine® and various generics), fexofenadine (Allegra® and various generics), and loratadine (Claritin® and various generics). A third generation antihistamine is desloratadine (Aerius®).