Astemizole
Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It has been withdrawn from the market in most countries because of rare but potentially fatal side effects (QTc interval prolongation and related arrhythmias due to hERG channel blockade).
Histamine
First-generation H antihistamines (i.e., antagonists of histamine receptor H) are capable of crossing the blood–brain barrier and produce drowsiness by antagonizing histamine H receptors in the tuberomammillary nucleus. The newer class of second-generation H antihistamines do not readily permeate the blood–brain barrier and thus are less likely to cause sedation, although individual reactions, concomitant medications and dosage may increase the likelihood of a sedating effect. In contrast, histamine H receptor antagonists increase wakefulness. Similar to the sedative effect of first-generation H antihistamines, an inability to maintain vigilance can occur from the inhibition of histamine biosynthesis or the loss (i.e., degeneration or destruction) of histamine-releasing neurons in the TMN.