Antihistamine
Antihistamine | |
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HRH4 | |
External links | |
MeSH | D006633 |
Legal status | |
In Wikidata |
Antihistamines are
Although people typically use the word "antihistamine" to describe drugs for treating allergies, doctors and scientists use the term to describe a class of drug that opposes the activity of histamine receptors in the body.[2] In this sense of the word, antihistamines are subclassified according to the histamine receptor that they act upon. The two largest classes of antihistamines are H1-antihistamines and H2-antihistamines.
H1-antihistamines work by binding to
Medical uses
Histamine makes blood vessels more permeable (
Antihistamines suppress the histamine-induced
Types
H1-antihistamines
H1-antihistamines refer to compounds that inhibit the activity of the
Clinically, H1-antihistamines are used to treat
A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation antihistamines having
List of H1 antagonists/inverse agonists
- Acrivastine
- Alimemazine (a phenothiazine used as antipruritic, antiemetic and sedative)
- Amitriptyline (tricyclic antidepressant)
- Amoxapine (tricyclic antidepressant)
- Aripiprazole (atypical antipsychotic, trade name: Abilify)
- Azelastine
- Bilastine
- Bromodiphenhydramine(Bromazine)
- Brompheniramine
- Buclizine
- Carbinoxamine
- Cetirizine (Zyrtec)
- Chlophedianol(Clofedanol)
- Chlorodiphenhydramine[12]
- Chlorpheniramine
- Chlorpromazine (low-potency typical antipsychotic, also used as an antiemetic)
- Chlorprothixene (low-potency typical antipsychotic, trade name: Truxal)
- Chloropyramine (first generation antihistamine marketed in Eastern Europe)
- Cinnarizine (also used for motion sickness and vertigo)
- Clemastine
- Clomipramine (tricyclic antidepressant)
- Clozapine (atypical antipsychotic; trade name: Clozaril)
- Cyclizine
- Cyproheptadine
- Desloratadine
- Dexbrompheniramine
- Dexchlorpheniramine
- Dimenhydrinate (used as an antiemetic and for motion sickness)
- Dimetindene
- Diphenhydramine (Benadryl)
- Dosulepin (tricyclic antidepressant)
- Doxepin (tricyclic antidepressant)
- Doxylamine (most commonly used as an over-the-counter sedative)
- Ebastine
- Embramine
- Fexofenadine (Allegra/Telfast)
- Fluoxetine
- Hydroxyzine (also used as an anxiolytic and for motion sickness; trade names: Atarax, Vistaril)
- Imipramine (tricyclic antidepressant)
- Ketotifen
- Levocabastine (Livostin/Livocab)
- Levocetirizine (Xyzal)
- Levomepromazine (low-potency typical antipsychotic)
- Loratadine (Claritin)
- Maprotiline (tetracyclic antidepressant)
- Meclizine (most commonly used as an antiemetic)
- Mianserin (tetracyclic antidepressant)
- Mirtazapine (tetracyclic antidepressant, also has antiemetic and appetite-stimulating effects; trade name: Remeron)
- Olanzapine (atypical antipsychotic; trade name: Zyprexa)
- Olopatadine (used locally)
- Orphenadrine (a close relative of diphenhydramine used mainly as a skeletal muscle relaxant and anti-Parkinsons agent)
- Periciazine (low-potency typical antipsychotic)
- Phenindamine
- Pheniramine
- Phenyltoloxamine
- Promethazine (Phenergan)
- Pyrilamine(crosses the blood–brain barrier; produces drowsiness)
- Quetiapine (atypical antipsychotic; trade name: Seroquel)
- Rupatadine (Alergoliber)
- Setastine (Loderix)
- Setiptiline (or teciptiline, a tetracyclic antidepressant, trade name: Tecipul)
- Trazodone (SARI antidepressant/anxiolytic/hypnotic with mild H1 blockade action)
- Tripelennamine
- Triprolidine
H2-antihistamines
H2-antihistamines, like H1-antihistamines, exist as inverse agonists and neutral antagonists. They act on H2 histamine receptors found mainly 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 inhibit H2 signaling thus reduce the secretion of gastric acid.
H2-antihistamines are among first-line therapy to treat
Examples include:
- Cimetidine
- Famotidine
- Lafutidine
- Nizatidine
- Ranitidine
- Roxatidine
- Tiotidine
H3-antihistamines
An H3-antihistamine is a classification of
Examples of selective H3-antihistamines include:
H4-antihistamines
H4-antihistamines inhibit the activity of the H4 receptor. Examples:
- Thioperamide
- JNJ 7777120
- VUF-6002
Atypical antihistamines
Histidine decarboxylase inhibitors
Inhibit the action of histidine decarboxylase:
Mast cell stabilizers
Mast cell stabilizers are drugs which prevent mast cell degranulation.
- Cromolyn sodium
- Nedocromil
- β-agonists
History
The first H1 receptor antagonists were discovered in the 1930s and were marketed in the 1940s.[17] Piperoxan was discovered in 1933 and was the first compound with antihistamine effects to be identified.[17] Piperoxan and its analogues were too toxic to be used in humans.[17] Phenbenzamine (Antergan) was the first clinically useful antihistamine and was introduced for medical use in 1942.[17] Subsequently, many other antihistamines were developed and marketed.[17] Diphenhydramine (Benadryl) was synthesized in 1943, tripelennamine (Pyribenzamine) was patented in 1946, and promethazine (Phenergan) was synthesized in 1947 and launched in 1949.[17][18][19] By 1950, at least 20 antihistamines had been marketed.[20] Chlorphenamine (Piriton), a less sedating antihistamine, was synthesized in 1951, and hydroxyzine (Atarax, Vistaril), an antihistamine used specifically as a sedative and tranquilizer, was developed in 1956.[17][21] The first non-sedating antihistamine was terfenadine (Seldane) and was developed in 1973.[17][22] Subsequently, other non-sedating antihistamines like loratadine (Claritin), cetirizine (Zyrtec), and fexofenadine (Allegra) were developed and introduced.[17]
The introduction of the first-generation antihistamines marked the beginning of medical treatment of nasal allergies.
Society and culture
The United States government removed two second generation antihistamines, terfenadine and astemizole, from the market based on evidence that they could cause heart problems.[1]
Research
Not much published research exists which compares the efficacy and safety of the various antihistamines available.[1] The research which does exist is mostly short-term studies or studies which look at too few people to make general assumptions.[1] Another gap in the research is in information reporting the health effects for individuals with long-term allergies who take antihistamines for a long period of time.[1] Newer antihistamines have been demonstrated to be effective in treating hives.[1] However, there is no research comparing the relative efficacy of these drugs.[1]
Special populations
In 2020, the UK National Health Service wrote that "[m]ost people can safely take antihistamines" but that "[s]ome antihistamines may not be suitable" for young children, the pregnant or breastfeeding, for those taking other medicines, or people with conditions "such as heart disease, liver disease, kidney disease or epilepsy".[25]
Most studies of antihistamines reported on people who are younger, so the effects on people over age 65 are not as well understood.[1] Older people are more likely to experience drowsiness from antihistamine use than younger people.[1] Continuous and/or cumulative use of anticholinergic medications, including first-generation antihistamines, is associated with higher risk for cognitive decline and dementia in older people.[26][27]
Also, most of the research has been on caucasians and other ethnic groups are not as represented in the research.[1] The evidence does not report how antihistamines affect women differently than men.[1] Different studies have reported on antihistamine use in children, with various studies finding evidence that certain antihistamines could be used by children 2 years of age, and other drugs being safer for younger or older children.[1]
Potential uses studied
Research regarding the effects of commonly used medications upon certain cancer therapies has suggested that when consumed in conjunction with immune checkpoint inhibitors some may influence the response of subjects to that particular treatment whose T-cell functions were failing in anti-tumor activity. Upon study of records in mouse studies associated with 40 common medications ranging from antibiotics, antihistamines, aspirin, and hydrocortisone, that for subjects with melanoma and lung cancers, fexofenadine, one of three medications, along with loratadine, and cetirizine, that target histamine receptor H1 (HRH1), demonstrated significantly higher survival rates and had experienced restored T-cell anti-tumor activity, ultimately inhibiting tumor growth in the subject animals.[28] Such results encourage further study in order to see whether results in humans is similar in combating resistance to immunotherapy.
See also
References
- ^ a b c d e f g h i j k l m n o p q Consumer Reports (2013), Using Antihistamines to Treat Allergies, Hay Fever, & Hives - Comparing Effectiveness, Safety, and Price (PDF), Yonkers, New York: Consumer Reports, archived from the original (PDF) on 17 May 2017, retrieved 29 June 2017
- ^ PMID 23268457.
The H1-receptor is a transmembrane protein belonging to the G-protein coupled receptor family. Signal transduction from the extracellular to the intracellular environment occurs as the GCPR becomes activated after binding of a specific ligand or agonist. A subunit of the G-protein subsequently dissociates and affects intracellular messaging including downstream signaling accomplished through various intermediaries such as cyclic AMP, cyclic GMP, calcium, and nuclear factor kappa B (NF-κB), a ubiquitous transcription factor thought to play an important role in immune-cell chemotaxis, proinflammatory cytokine production, expression of cell adhesion molecules, and other allergic and inflammatory conditions.1,8,12,30–32 ... For example, the H1-receptor promotes NF-κB in both a constitutive and agonist-dependent manner and all clinically available H1-antihistamines inhibit constitutive H1-receptor-mediated NF-κB production ...
Importantly, because antihistamines can theoretically behave as inverse agonists or neutral antagonists, they are more properly described as H1-antihistamines rather than H1-receptor antagonists.15 - PMID 26084539.
- ^ S2CID 11849647.
- ^ a b c d "H1 receptor". IUPHAR/BPS Guide to Pharmacology. Retrieved 8 October 2015.
- PMID 7540412.
- ^ "Best Antihistamine for Tinnitus?". Tinnitus and You. 28 September 2021. Retrieved 15 March 2022.
- PMID 9042073.
- S2CID 3406128.
- PMID 27015774.
- PMID 23282332.
- OCLC 1127763671.
- PMID 18278935.
- S2CID 15430117.
- PMID 9808693. Archived from the originalon 2 May 2020. Retrieved 9 August 2014.
- PMID 15294456.
- ^ ISBN 978-0-941901-21-5.
- ISBN 978-0-674-03845-5.
- ISBN 978-3-527-63212-1.
- ISBN 978-1-137-27743-5.
- ISBN 978-1-68108-337-7.
- ISBN 978-0-470-01552-0.
- PMID 25582156.
- ^ S2CID 29402462.
- ^ "Antihistamines". NHS. 28 February 2020. Archived from the original on 22 December 2017. Retrieved 28 April 2021.
- PMID 25621434.
- PMID 19636034.
- ^ Manjarrez, Alejandra Manjarrez, Over-the-Counter Antihistamines Could Help Against Cancer, The Scientist, November 24, 2021
External links
- Histamine+antagonist at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Antihistamine Archived 22 April 2017 at the Wayback Machine information at Allergy UK