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'''Histamine''' is a compound involved in local [[immune system|immune responses]], regulates the [[gastrointestinal system|gut]], and acts as a [[neurotransmitter]]. Histamine is released by [[mast cell]]s and excess histamine is involved in many of the symptoms of [[mast cell activation disorder]]. '''Histamine dihydrochloride''' is an immunostimulant drug sold under the brand name '''Ceplene''' for acute myeloid leukemia.<ref name="pubchem">{{Cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/774 | title = Histamine | last = | first = | authorlink = | date = | website = PubChem|language=en|archive-url=|archive-date=|url-status=|access-date=2022-01-06}}</ref> ==Types of histamine receptors== All known histamine receptors are G-coupled.<ref name="NBK557790" /> ===H1 receptor=== Location: *[[neuron]]s *smooth muscle cells of the airways *blood vessels *widespread throughout the body<ref name="NBK557790" /> ===H2 receptor=== Location: mostly in *gastric mucosa parietal cells *smooth muscle cells *heart<ref name="NBK557790" /> ===H3 receptor=== Location: *mostly in histaminergic [[neuron]]s, which moderate histamine, [[dopamine]],[[serotonin]], [[noradrenaline]], and [[acetylcholine]] release in the [[central nervous system]]<ref name="NBK557790" /> ===H4 receptor=== Location: *bone marrow *peripheral hematopoietic cells<ref name="NBK557790">{{Cite book | title = Biochemistry, Histamine | date = 2021 | url=http://www.ncbi.nlm.nih.gov/books/NBK557790/ | last = Patel | first = Raj H. | last2 = Mohiuddin | first2 = Shamim S.|location=Treasure Island (FL)| publisher = StatPearls Publishing|pmid=32491722}}</ref> ==Role of histamine in the body== Histamine stimulates [[inflammation]] by increasing blood flow to a site of infection or the region surrounding allergens, so your immune can engulf the foreign particle. It does this by causing the release of [[nitric oxide]], which in turn causes [[vasodilation]].{{citation needed}} ==Modulating histamine levels== Histamine is broken down by an enzyme called [[diamine oxidase]] (DAO), which is found mainly in the [[gastrointestinal tract]] and in [[pregnant]] women, the [[placenta]]. Nutritional deficiencies in [[Vitamin C]], [[magnesium]], [[Vitamin B6]] and [[copper]] – all DAO cofactors – can decrease DAO activity. [[Vitamin C]] reduces blood histamine levels,<ref name="clemetson1980">{{Citation| issn = 0022-3166| volume = 110 | issue = 4| pages = 662–668| last = Clemetson | first = C.A. | title = Histamine and ascorbic acid in human blood| journal = The Journal of Nutrition | date = April 1980 | pmid = 7365537}}</ref><ref name="johnston1992">{{Citation| issn = 0731-5724| volume = 11 | issue = 2| pages = 172–176| last1 = Johnston | first1 = C.S. | last2 = Martin | first2 = L.J. | last3 = Cai | first3 = X.| title = Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis| journal = Journal of the American College of Nutrition | date = April 1992 | pmid = 1578094}}</ref><ref>{{Cite journal | last = Johnston | first = CS | date = December 1996 | title = Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults | url = https://www.ncbi.nlm.nih.gov/pubmed/8951736|journal=J Am Coll Nutr.|volume=|pages=|via=}}</ref> potentially through several mechanisms: by inhibiting mast cell production; by increasing [[diamine oxidase]] (an [[enzyme]] that breaks down histamine); by inhibiting mast cell degranulation (and the release of histamine in the first place),<ref name=":0">{{Cite journal | last = Mio | first = M | date = 1999 | title = Ultraviolet B (UVB) light-induced histamine release from rat peritoneal mast cells and its augmentation by certain phenothiazine compounds | url = https://www.sciencedirect.com/science/article/pii/S0162310998000538|journal=Immunopharmacology|volume=|pages=|via=}}</ref> and by inhibiting [[histidine decarboxylase]] (the enzyme that forms histamine).<ref>{{Cite journal | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/ | title = Pharmacological treatment options for mast cell activation disease | last = Molderings | first = Gerhard | date = 2016 | journal=Naunyn Schmiedebergs Arch Pharmacol|volume=|pages=|via=}}</ref> [[Manganese]] and [[zinc]] can also prevent the release of histamine from [[mast cell]]s. == Histamine intolerance == Histamine sensitivity can be a sign of [[mast cell activation disorder]]. Histamine Intolerance (HI) is a separate diagnosis.<ref name="histamine-intolerance">{{Cite web | url=https://www.histamineintolerance.org.uk/ | title = Histamine Intolerance: Symptoms, Diagnosis and The Food List | website = Histamine Intolerance|language=en-GB|access-date=2022-01-06}}</ref> {{See also|Histamine intolerance}} == Antihistamines == Antihistamines, also known as histamine antagonists help block the effects of histamine in the body. Classic antihistamines block H1 histamine receptors only.<ref name="antagonists">{{Cite web | url=https://go.drugbank.com/categories/DBCAT000664 | title = Histamine Antagonists | last = | first = | authorlink = | date = | website = DrugBank Online|archive-url=|archive-date=|url-status=|access-date=2021-02-18}}</ref> Antihistamines include: ===H1 receptor antihistamines=== *[[Cinnarizine]] - sedating *[[Diphenhydramine]] (some Benadryl products) - sedating *[[Hydroxyzine]] (Atarax/Vistaril) - sedating *[[Ketotifen]] - (Zaditor or Zaditen) - sedating, also a [[:Category:Mast cell stabilizers|mast cell stabilizer]] *[[Promethazine]] (Phenergan) - Sedating *[[Triprolidine]] (Actifed) - sedating *[[Acrivastine]] (some Benadryl products) *[[Cetirizine]] (Zyrtec, some Benadryl products) *[[Chlorpheniramine maleate]] (Piriton) *[[Fexofenadine]] (Allegra) *[[Loratadine]] (Claritin) *[[Meclizine]] (antihistamine) * many others also exist<ref name="NBK557790" /><ref name="H1-antagonists">{{Cite web | url=https://go.drugbank.com/categories/DBCAT000665 | title = Histamine H1 Antagonists | last = | first = | authorlink = | date = | website = DrugBank Online|archive-url=|archive-date=|url-status=|access-date=2022-01-06}}</ref><ref name="NZ-antihistamines">{{Cite web | url=https://www.medsafe.govt.nz/profs/class/Agendas/agen30-MohAntihistamines.pdf | title=Classification of Antihistamines | last = | first = | authorlink = | date = | website = Medsafe - Government of New Zealand|archive-url=|archive-date=|url-status=|access-date=2022-01-06}}</ref> Uses of various H1 antagonists include: * [[allergy|allergies]], sometimes including [[anaphylaxis]] * [[asthma]] * [[eczema]] * [[insomnia]] * [[skin itch|itching]] including pruritus and urticaria * [[nausea]] and [[vomiting]] * [[vertigo]] * travel sickness * [[vertigo]]<ref name="H1-antagonists" /> ===H2 receptor antihistamines=== *[[Cimetidine]] (Tagament) - also blocks androgenic [[testosterone]] at high doses *[[Famotidine]] (Pepcid) - under investigation for [[Long COVID]] *[[Nizatidine]] (Axid) *[[Ranitidine]] (Zantac) - withdrawn from US market in 2020<ref name="NBK557790" /><ref name="medline-h2">{{Cite web | url = https://medlineplus.gov/ency/patientinstructions/000382.htm | title = H2 blockers | website = H2 blockers: MedlinePlus Medical Encyclopedia|access-date=2022-01-06}}</ref><ref name="rantidine">{{Cite web | url = https://www.drugs.com/ranitidine.html | title = Rantidine|website=drugs.com|access-date=2022-01-06}}</ref> ===H3 receptor antihistamines=== *[[Pitolisant]] (Wakix) which is licensed for narcolepsy<ref name="Pitolisant-H3">{{Cite journal | title = Pitolisant and Other Histamine-3 Receptor Antagonists—An Update on Therapeutic Potentials and Clinical Prospects | date = 2020-09-01 | url = https://doi.org/10.3390/medicines7090055|journal=Medicines|volume=7|issue=9 | pages = 55 | last = Harwell | first = Victoria | last2 = Fasinu | first2 = Pius|doi=10.3390/medicines7090055|pmc=PMC7554886|pmid=32882898|issn=2305-6320}}</ref> *[[Betahistine]] (Serc) - typically used for [[vertigo]] and [[Ménière's disease]]<ref>{{Cite web | title = Betahistine HCI: Summary Report | date = Dec 2019 | url = https://archive.hshsl.umaryland.edu/bitstream/handle/10713/12065/Betahistine%20HCl_Final_2019_12.pdf?sequence=6&isAllowed=y | last = Yuen | first = Melissa V. | authorlink = | last2 = Gianturco | first2 = Stephanie L. | authorlink2 = | last3 = Pavlech | first3 = Laura L. | authorlink3 = | last4 = Storm | first4 = KathenaD. | authorlink4 = | last5 = Yoon | first5 = SeJeong | authorlink5 = | last6 = Mattingly | first6 = Ashlee N. | authorlink6 = | publisher = University of Maryland Center of Excellence for Science and Innovation|access-date=2022-01-06|quote=|via=}}</ref> (EU, UK, Australia) but not FDA approved *[[Ciproxifan]] and [[thioperamide]] - not in clinical use<ref name="Lin2011" /> H3R antagonists are being investigated for potential use in treatmenting of neurodegenerative diseases and sleep disorders, may reduce [[neuroinflammation]] and reduce [[cognitive dysfunction]].<ref name="NBK557790" /><ref name="Lin2011">{{Cite journal | title = Histamine H3 receptors and sleep-wake regulation | date = Jan 2011 | url = https://www.researchgate.net/profile/Jian-Sheng-Lin/publication/46413806_Histamine_H-3_Receptors_and_Sleep-Wake_Regulation/links/02e7e51a8eaff6f551000000/Histamine-H-3-Receptors-and-Sleep-Wake-Regulation.pdf | journal=The Journal of Pharmacology and Experimental Therapeutics|volume=336|issue=1|pages=17–23 | last = Lin | first = Jian-Sheng | authorlink = | last2 = Sergeeva | first2 = Olga A. | authorlink2 = | last3 = Haas | first3 = Helmut L. | authorlink3 = |doi=10.1124/jpet.110.170134|pmc=|pmid=20864502|access-date=|issn=1521-0103|quote=|via=}}</ref> ===H4 receptor antihistamines=== H4R antagonists are being investigated for use in allergies, and inflammatory conditions such as hayfever, chronic [[skin itch|pruritus]], and asthma.<ref name="NBK557790" /> ==See also== *[[:Category:Antihistamines|Antihistamines]] (category) *[[Diamine oxidase]] *[[Low histamine diet]] *[[Histamine N-methyltransferase]] *[[Mast cell activation syndrome]] *[[Mast cell activation disorder]] ==Learn more== *[https://go.drugbank.com/categories/DBCAT000665 H1 Histamine Antagonists] - DrugsBank Online *[https://go.drugbank.com/categories/DBCAT000933 H2 Histamine Antagonists] - DrugsBank Online *[https://www.ncbi.nlm.nih.gov/books/NBK557790/ Biochemistry, Histamine] - StatPearls *[https://www.drugs.com/ranitidine.htm Rantidine] - drugs.com ==References== {{Reflist}} [[Category:Biochemistry and cell biology]] [[Category:Neurotransmitters and hormones]] [[Category:Immunostimulants]] [[Category:Neurotransmitters]]
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