Main unwanted side effect of sedating antihistamines
This superfamily represents at least 500 individual membrane proteins that share a common structural motif of 7 transmembrane α-helical segments[7, 8] (Figure 1A).
The histamine HA, Diagram of a histamine H1-receptor in a membrane showing the 7 transmembrane domains.
In February 2009, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom advised that cough and cold remedies containing certain ingredients, including first-generation H-antihistamines, should no longer be used in children younger than 6 years because the balance of benefit and risks has not been shown to be favorable.
Reports submitted to regulators stated that more than 3000 people have reported adverse reactions to these drugs and that diphenhydramine and chlorpheniramine were mentioned in reports of 27 and 11 deaths, respectively.-antihistamine, patients seek attributes that include good efficacy, a rapid onset of action, a long duration of action, and freedom from unwanted effects.
During this time, knowledge of the nature and diversity of receptors was rudimentary to say the least and it was only several decades later that the existence of more than one species of histamine receptor was discovered.
This review will concentrate on the histamine H-receptor is a member of the superfamily of G-protein coupled receptors.
Desloratadine is the most potent antihistamine (Ki 0.4 n M) followed by levocetirizine (Ki 3 n M) and fexofenadine (Ki 10 n M) (the lower the concentration, the higher potency).
Although these are often considered to be fixed values, they may be influenced by temperature and p H, and therefore, they can differ in physiologic and pathologic conditions.
Histamine is an important neuromediator in the human brain which contains approximately 64,000 histamine-producing neurones, located in the tuberomamillary nucleus.H-antihistamines, which are not structurally related to histamine, do not antagonize the binding of histamine but bind to different sites on the receptor to produce the opposite effect.For example, cetirizine cross-links sites on transmembrane domains IV and VI to stabilize the receptor in the inactive state and swing the equilibrium to the off position (Figure 1C).Physiologically, the release of histamine during the day causes arousal whereas its decreased production at night results in a passive reduction of the arousal response.When taken during the day, first-generation H-antihistamines, even in the manufacturers' recommended doses, frequently cause daytime somnolence, sedation, drowsiness, fatigue, and impaired concentration and memory[17, 18].