Histamine antagonist
A histamine antagonist is an agent that inhibits action of histamine via histamine receptors. H1 antihistamines are used as treatment for symptoms of allergies such as runny nose. Allergies are caused by an excessive type 1 hypersensitivity response of the body to allergens, such as pollen released by plants. An allergic reaction, which if severe enough can lead to anaphylaxis, results in excessive release of histamines and other mediators by the body. Other uses of H1 antihistamines help with symptoms of local inflammation that results from various conditions, such as insect stings, even if there is no allergic reaction. Other commonly used examples of antihistamines include the H2 antagonists (Cimetidine) which are widely used for the treatment of acid reflux and stomach ulcers as they decrease gastric acid production.
Clinical effects
Histamines will 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 flare (vasodilation) 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 antagonistIn 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.
Examples:
- Clemastine
- Diphenhydramine (Benadryl)
- Doxylamine (most commonly used as an OTC sedative)
- Loratadine
- Desloratadine
- Fexofenadine
- Pheniramine
- Cetirizine
- Ebastine
- Promethazine
- Chlorpheniramine
- Levocetirizine
- Olopatadine (used locally)
- Quetiapine (antipsychotic)
- Meclizine (most commonly used as an antiemetic)
- Dimenhydrinate (most commonly used as an antiemetic)
H2-receptor antagonists
Main article:
H2 antagonistH2 antagonists, like H1 antagonists, are also inverse agonists and not true antagonists. H2 histamine receptors are found principally in the parietal cells of the gastric mucosa. H2 antagonists are used to reduce the secretion of gastric acid, treating gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease.
Examples:
- Cimetidine
- Famotidine
- Ranitidine
- Nizatidine
- Roxatidine
- Lafutidine
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 antiinflammatory and analgesic drugs.
H3-receptor antagonists
Examples:
- A-349,821
- ABT-239
- Ciproxifan
- Clobenpropit
- Thioperamide
H4-receptor antagonists
Examples:
- Thioperamide
- JNJ 7777120
- VUF-6002
Others
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.[4]
References
- ↑ 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.
- ↑ Sicherer, Scott H. M.D., Understanding and Managing Your Child's Food Allergy. Baltimore: The Johns Hopkins University Press, 2006.
- ↑ 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.
- ↑ Klenner, Frederick R. Observations On the Dose and Administration of Ascorbic Acid.... Section "Ascorbic acid to the rescue."
External links
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Antihistamines (R06) |
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| Aminoalkyl ethers |
Bromazine/Bromodiphenhydramine • Carbinoxamine • Clemastine • Chlorphenoxamine • Diphenylpyraline • Diphenhydramine • Doxylamine • Orphenadrine • Phenyltoloxamine |
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H1
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Agonists: 2-Pyridylethylamine • Betahistine • Histamine • HTMT • UR-AK49
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Agonists: Amthamine • Betazole • Dimaprit • Histamine • HTMT • Impromidine • UR-AK49
Antagonists: Bisfentidine • Burimamide • Cimetidine • Dalcotidine • Donetidine • Ebrotidine • Etintidine • Famotidine • Lafutidine • Lamtidine • Lavoltidine/Loxtidine • Lupitidine • Metiamide • Mifentidine • Niperotidine • Nizatidine • Osutidine • Oxmetidine • Pibutidine • Quisultidine/Quisultazine • Ramixotidine • Ranitidine • Roxatidine • Sufotidine • Tiotidine • Tuvatidine • Venritidine • Zaltidine
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H3
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Agonists: α-Methylhistamine • Cipralisant • Histamine • Imetit • Immepip • Immethridine • Methimepip • Proxyfan
Antagonists: A-349,821 • A-423,579 • ABT-239 • Betahistine • Burimamide • Ciproxifan • Clobenpropit • Conessine • GSK-189,254 • Impentamine • Iodophenpropit • JNJ-5,207,852 • MK-0249 • NNC-38-1,049 • PF-03654746 • SCH-79,687 • Thioperamide • Tiprolisant • VUF-5,681
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H4
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Agonists: 4-Methylhistamine • Histamine • VUF-8,430
Antagonists: JNJ-7,777,120 • Thioperamide • VUF-6,002
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