Antihistamines have a broad range of functions -- they can ease allergy symptoms, alleviate gastrointestinal complaints, prevent motion sickness and aid in sleep, to name just a few. Antihistamines accomplish these tasks by counteracting histamine, an important protein with diverse effects in the body. Histamine acts by binding to other proteins called histamine receptors, which are found on the surface of various types of cells. The receptors are the "locks" that are opened by the "key," histamine. Opening the “lock” initiates a series of reactions within the cells that ultimately lead to histamine’s effects. Antihistamines are commonly classified according to the type of histamine receptor they block.
First Generation H1-Receptor Blockers
The first antihistamines, developed a few decades after the discovery of histamine, block a receptor for histamine known as the H1-receptor. These can be thought of as the "old-fashioned" group of antihistamines. Diphenhydramine (Benadryl) is one of the most common first generation H1-receptor blockers. Other examples include clemastine (Tavist), dimenhydrinate (Dramamine), promethazine (Phenergan) and hydroxyzine (Vistaril, Atarax).
Second Generation H1-Receptor Blockers
Since histamine functions to help keep people awake, the first generation H1-receptor antagonists tend to cause drowsiness. While this is desirable when anithistamines are used as sleep aids, it is a clear disadvantage when these medications are used for other purposes, such as for daytime relief of allergies. In response, researchers developed a new group of H1-receptor antihistamines that do not pass easily into the brain. Because of this, these second generation H1-receptor blockers produce less sleepiness. Common examples of these newer drugs include loratadine (Claritin), fexofenadine (Allegra) and terfenadine (Seldane).
H2-, H3- and H4-Receptor Blockers
Antihistamines have also been developed to block histamine receptors other than H1. H2-receptor blockers -- also known as H2-blockers -- are largely used to reduce acid production in the stomach. These include such common drugs as cimetidine (Tagamet), famotidine (Pepsid, Fluxid), ranitidine (Zantac) and nizatidine (Axid). Several H3-receptor blockers and H4-receptor blockers are under development, but have not yet been approved for use by the US Food and Drug Administration. H3-receptor blockers, such as ciproxifan, may be useful for such conditions as ADHD and Alzheimer's disease.
Histamine Release Inhibitors
Other types of antihistamines work by mechanisms completely different from the histamine receptor blockers. Instead of acting at histamine receptors, histamine release inhibitors prevent the release of histamine from mast cells. These cells release histamine in response to exposure to allergens. Histamine release inhibitors -- also known as mast cell stabilizers -- are primarily used for the prevention of allergy symptoms. Sodium cromoglycate (Intal) is the most common histamine release inhibitor.
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