As the name suggests, First-generation antihistamines, such as chlorpheniramine and diphenhydramine were the first kind to get approved by the Food and Drug Administration (FDA), and became available on the market in the early 1940s. Second-generation antihistamines, like fexofenadine (the active ingredient in Histallay), became available for general use in the 1980s. One of the key attributes of first-generation antihistamines that differentiate them from second-generation antihistamines is that they cross your blood-brain barrier (BBB) that results in drowsiness.