Histamine antagonist

A histamine antagonist, commonly referred to as antihistamine, is a pharmaceutical drug that inhibits action of histamine by blocking it from attaching to histamine receptors.

Clinical effects
Histamines produce increased vascular permeability, causing fluid to escape from capillaries into the tissues, which leads to the classic symptoms of an allergic reaction – a runny nose and watery eyes.

Antihistamines suppress the histamine-induced wheal (swelling) and vasodilation (flare) response by blocking the binding of histamine to its receptors on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells. They effectively exert competitive antagonism of histamine for H1-receptors. Itching and sneezing are suppressed by antihistamine blockade of H1-receptors on nasal sensory nerves. Antihistamines are commonly used for relief of allergies caused by intolerances of proteins.

H1-receptor antagonists
In common use, the term antihistamine refers only to H1 antagonists, also known as H1 antihistamines. It has been discovered that these H1-antihistamines are actually inverse agonists at the histamine H1-receptor, rather than antagonists per se. Clinically, H1 antagonists are used to treat allergic reactions. Sedation is a common side effect, and some H1 antagonists, such as diphenhydramine and doxylamine, are also used to treat insomnia. However, second generation antihistamines do not cross the blood brain barrier, and as such do not cause drowsiness.

Examples:
 * Azelastine
 * Cetirizine
 * Cyclizine
 * Chlorpheniramine
 * Clemastine
 * Desloratadine
 * Dexchlorpheniramine
 * Dimenhydrinate (most commonly used as an antiemetic)
 * Dimetindene
 * Diphenhydramine (Benadryl)
 * Doxylamine (most commonly used as an OTC sedative)
 * Ebastine
 * Embramine
 * Fexofenadine
 * Levocetirizine
 * Loratadine
 * Meclozine (most commonly used as an antiemetic)
 * Olopatadine (used locally)
 * Pheniramine
 * Promethazine
 * Quetiapine (antipsychotic)

H2-receptor antagonists
H2 antagonists, like H1 antagonists, are also inverse agonists and not true antagonists. H2 histamine receptors, found principally in the parietal cells of the gastric mucosa, are used to reduce the secretion of gastric acid, treating gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease.

Examples:
 * Cimetidine
 * Famotidine
 * Lafutidine
 * Nizatidine
 * Ranitidine
 * Roxatidine

Experimental: H3- and H4-receptor antagonists
These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H3-antagonists have a stimulant and nootropic effect, and are being investigated for the treatment of conditions such as ADHD, Alzheimer's disease, and schizophrenia, whereas H4-antagonists appear to have an immunomodulatory role and are being investigated as anti-inflammatory and analgesic drugs.

H3-receptor antagonists
Examples:
 * A-349,821
 * ABT-239
 * Ciproxifan
 * Clobenpropit
 * Thioperamide

H4-receptor antagonists
Examples:
 * Thioperamide
 * JNJ 7777120
 * VUF-6002

Mast cell stabilizers
Mast cell stabilizers appear to stabilize the mast cells to prevent degranulation and mediator release. These drugs are not usually classified as histamine antagonists, but have similar indications.

Examples:
 * Cromoglicate (cromolyn)
 * Nedocromil
 * β2 adrenergic agonists

Other agents with antihistaminergic activity
Many drugs used for other indications possess unwanted antihistaminergic activity.

Large doses of vitamin C are known to alleviate shock by inhibiting deaminizing proteins that release histamine.