A histamine antagonist (commonly called an antihistamine) is a pharmaceutical drug that inhibits the action of histamine by either blocking its attachment to histamine receptors, or inhibiting the enzymatic activity of histidine decarboxylase; catalyzing the transformation of histidine into histamine (atypical antihistaminics). It is commonly used for the relief of allergies caused by intolerance of proteins.[1]

Clinical effects

Histamines produce increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and watery eyes. Histamine also promotes angiogenesis.

Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells. They exert a competitive antagonism to histamines.

Itching and sneezing are suppressed by antihistamine blocking of H1-receptors on nasal sensory nerves.[2] Antihistamines have also been used with great success in the treatment of Brown Recluse (genus Loxosceles) spider bites as well as other insect bites that cause necrosis.[3]

Clinical: H1- and H2-receptor antagonists

H1-receptor antagonists

Main article: H1 antagonist

In common use, the term antihistamine refers only to compounds that inhibit action at the H1 receptor (and not H2, etc).

Rather than "true" antagonists, H1-antihistamines are actually inverse agonists at the histamine H1-receptor.[4] 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.

It is commonly believed that second-generation antihistamines do not cross the blood–brain barrier, and as such are not supposed to cause drowsiness. However, this is not entirely correct. Some or most of the second-generation antihistamines are able to cross the blood-brain barrier, though in vastly smaller quantities. This allows second-generation antihistamines to exert their effects almost entirely on peripheral histamine receptors. However, since some can still effect the CNS drowsiness still may occur when second-generation antihistamines are used in higher doses.


H2-receptor antagonists

Main article: H2 antagonist

H2 antagonists, like H1 antagonists, are also inverse agonists and not true antagonists. They act on H2 histamine receptors found principally in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H2 to stimulate acid secretion; drugs that block H2 signaling thus reduce the secretion of gastric acid. H2 antagonists are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses.


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

Main article: H3 antagonist


H4-receptor antagonists



Atypical antihistaminics

They inhibit the enzymatic activity of histidine decarboxylase :

Mast cell stabilizers

Main article: Mast cell stabilizer

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.


Other agents with antihistaminergic activity

Many drugs used for other indications possess unwanted antihistaminergic activity.


External links

  • Medical Subject Headings (MeSH)