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.^[1] Antihistamines are commonly used for relief of allergies caused by intolerances of proteins.^[2]

Clinical: H₁- and H₂-receptor antagonists

H₁-receptor antagonists

Main article: H₁ antagonist

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.^[3] 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)
• Rupatadine

H₂-receptor antagonists

Main article: H₂ antagonist

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

Main article: H₃ antagonist

Examples:

• A-349,821
• ABT-239
• Ciproxifan
• Clobenpropit
• Thioperamide

H₄-receptor antagonists

Examples:

• Thioperamide
• JNJ 7777120
• VUF-6002

Others

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.

Examples:

• Cromoglicate (cromolyn)
• Nedocromil
• β2 adrenergic agonists

Other agents with antihistaminergic activity

Many drugs used for other indications possess unwanted antihistaminergic activity.^{[citation needed]}

References

1. ^ Monroe, E., MD, Daly, A., and Shalhoub, R., MD. 1997. Appraisal of the validity of histmine-induced wheal and flare is used to predict the clinical efficacy of antihistamines. The Journal of Allergy and Clinical Immunology 99(2): S789-806.
2. ^ Sicherer, Scott H. M.D., Understanding and Managing Your Child's Food Allergy. Baltimore: The Johns Hopkins University Press, 2006.
3. ^ Leurs R, Church MK, Taglialatela M (2002). "H₁-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects". Clin Exp Allergy 32 (4): 489–98. doi:10.1046/j.0954-7894.2002.01314.x. PMID 11972592. 

External links

• MeSH Histamine+antagonist