View source for Tyramine

{{Short description|Chemical compound}}
{{distinguish|Amphetamine{{!}}thyramine}}
{{Use dmy dates|date=March 2014}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| verifiedrevid = 
| image = Tyramine.svg
| image_class = skin-invert-image
| width = 
| caption = [[Skeletal formula]] of tyramine
| image2 = Tyramine-neutral-from-xtal-view-1-3D-bs-17.png
| image_class2 = bg-transparent 
| caption2 = [[Ball-and-stick model]] of the neutral (non-[[zwitterion]]ic) form of tyramine found in the [[crystal structure]]<ref>{{ cite journal | title = Tautomeric and ionisation forms of dopamine and tyramine in the solid state | vauthors = Cruickshank L, Kennedy AR, Shankland N | journal = [[Journal of Molecular Structure|J. Mol. Struct.]] | volume = 1051 | pages = 132–136 | year = 2013 | doi = 10.1016/j.molstruc.2013.08.002 | bibcode = 2013JMoSt1051..132C }}</ref>
| width2 =

<!-- Clinical data -->
| pronounce = {{IPAc-en|ˈ|t|aɪ|r|ə|m|iː|n}} {{respell|TY|rə|meen}}
| tradename = 
| Drugs.com = 
| MedlinePlus = 
| pregnancy_AU = <!-- A/B1/B2/B3/C/D/X -->
| pregnancy_AU_comment = 
| pregnancy_US = <!-- A/B/C/D/X/N -->
| pregnancy_category = 
| routes_of_administration =

<!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_AU_comment = 
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_DE = <!-- Anlage I, II, III -->
| legal_NZ = <!-- Class A, B, C -->
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_US = <!-- OTC/Rx-only/Schedule I, II, III, IV, V -->
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_status =

<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 
| metabolism = [[CYP2D6]], [[flavin-containing monooxygenase 3]], [[monoamine oxidase A]], [[monoamine oxidase B]], [[phenylethanolamine N-methyltransferase|phenylethanolamine ''N''-methyltransferase]], [[dopamine beta-hydroxylase|dopamine β-hydroxylase]], others
| metabolites = <!-- from http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=2150 -->[[4-Hydroxyphenylacetaldehyde]], [[dopamine]], [[N-methyltyramine|''N''-methyltyramine]], [[octopamine]]
| onset = 
| elimination_half-life = 
| duration_of_action = 
| excretion =

<!-- Identifiers -->
| CAS_number = 51-67-2
| CAS_number_Ref = {{cascite|correct|CAS}}
| ATC_prefix = none
| ATC_suffix = 
| PubChem = 5610
| DrugBank = 
| IUPHAR_ligand = 2150
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5408
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = X8ZC7V0OX3
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C00483
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 11608
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 15760
| synonyms = Tyramin; 4-Hydroxyphenethylamine; ''para''-Tyramine; ''p''-Tyramine; 4-Tyramine; Mydrial; Uteramin

<!-- Chemical data -->
| IUPAC_name = 4-(2-aminoethyl)phenol
| C=8 | H=11 | N=1 | O=1
| SMILES = Oc1ccc(cc1)CCN
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C8H11NO/c9-6-5-7-1-3-8(10)4-2-7/h1-4,10H,5-6,9H2
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DZGWFCGJZKJUFP-UHFFFAOYSA-N

<!-- Physical data -->
| density = 1.103
| density_notes = predicted<ref>SciFinder, Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (© 1994-2021 ACD/Labs)</ref>
| boiling_point = 206
| boiling_notes = at 25&nbsp;mmHg; 166&nbsp;°C at 2&nbsp;mmHg<ref name = Merck/>
| melting_point = 164.5
| melting_notes = <ref name = Merck>The Merck Index, 10th Ed. (1983), p. 1405, Rahway: Merck & Co.</ref>
}}

'''Tyramine''' ({{IPAc-en|ˈ|t|aɪ|r|ə|m|iː|n}} {{respell|TY|rə|meen}}) (also spelled '''tyramin'''), also known under several other names,{{#tag:ref|Synonyms and alternative names include: '''4-hydroxyphenethylamine''', '''para-tyramine''', '''mydrial''', and '''uteramin'''; the latter two names are not commonly used. The [[IUPAC nomenclature of organic chemistry|IUPAC]] name is {{nowrap|4-(2-aminoethyl)phenol}}.|group="note"}} is a [[Natural product|naturally]] occurring [[trace amine]] derived from the amino acid [[tyrosine]].<ref name="pubchem">{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/5610|title=tyramine {{!}} C8H11NO|website=PubChem|language=en|access-date=2017-04-08}}</ref> Tyramine acts as a [[catecholamine]] [[Monoamine releasing agent|releasing agent]]. Notably, it is unable to cross the [[Blood–brain barrier|blood-brain barrier]], resulting in only non-psychoactive [[Peripheral nervous system|peripheral]] [[Sympathomimetic drug|sympathomimetic]] effects following ingestion. A [[Hypertensive emergency|hypertensive crisis]] can result, however, from ingestion of tyramine-rich foods in conjunction with the use of [[monoamine oxidase inhibitor]]s (MAOIs).

==Occurrence==
Tyramine occurs widely in [[plant]]s<ref>T. A. Smith (1977) ''Phytochemistry'' '''16''' 9–18.</ref> and [[animal]]s, and is metabolized by various [[enzyme]]s, including [[monoamine oxidase]]s. In foods, it often is produced by the [[decarboxylation]] of [[tyrosine]] during [[fermentation (food)|fermentation]] or [[Decomposition|decay]]. Foods that are fermented, cured, pickled, aged, or spoiled have high amounts of tyramine. Tyramine levels go up when foods are at room temperature or go past their freshness date.

Specific foods containing considerable amounts of tyramine include:<ref>{{cite web | vauthors = Hall-Flavin DK |title=Avoid the combination of high-tyramine foods and MAOIs |url=https://www.mayoclinic.org/diseases-conditions/depression/expert-answers/maois/faq-20058035 |website=Mayo Clinic |language=en |date=18 December 2018}}</ref><ref>{{cite web | vauthors = Robinson J |title=Tyramine-Rich Foods As A Migraine Trigger & Low Tyramine Diet |url=https://www.webmd.com/migraines-headaches/tyramine-and-migraines |website=WebMD |language=en |date=21 June 2020}}</ref>

* Strong or aged cheeses: cheddar, Swiss, Parmesan, Stilton, Gorgonzola or blue cheeses, Camembert, feta, Muenster
* Meats that are cured, smoked, or processed: such as salami, pepperoni, dry sausages, hot dogs, bologna, bacon, corned beef, pickled or smoked fish, caviar, aged chicken livers, soups or gravies made from meat extract
* Pickled or fermented foods: sauerkraut, kimchi, tofu (especially [[stinky tofu]]), pickles, miso soup, bean curd, tempeh, sourdough breads
* Condiments: soy, shrimp, fish, miso, teriyaki, and bouillon-based sauces
* Drinks: beer (especially tap or home-brewed), vermouth, red wine, sherry, liqueurs
* Beans, vegetables, and fruits: fermented or pickled vegetables, overripe fruits
* Chocolate<ref>{{cite web |title=Tyramine |url=https://pubchem.ncbi.nlm.nih.gov/compound/Tyramine#section=Mechanism-of-Action |website=pubchem.ncbi.nlm.nih.gov |language=en}}</ref>

Scientists more and more consider tyramine in food as an aspect of safety.<ref>{{cite journal | vauthors = Martuscelli M, Esposito L, Mastrocola D | title = Biogenic Amines' Content in Safe and Quality Food | journal = Foods | volume = 10 | issue = 1 | page = 100 | date = January 2021 | pmid = 33418895 | pmc = 7825060 | doi = 10.3390/foods10010100 | doi-access = free }}</ref> They propose projects of regulations aimed to enact control of biogenic amines in food by various strategies, including usage of proper fermentation starters, or preventing their decarboxylase activity.<ref>{{Cite journal |title=Scientific Opinion on risk based control of biogenic amine formation in fermented foods |journal=EFSA Journal |year=2011 |volume=9 |issue=10 |page=2393 |doi=10.2903/j.efsa.2011.2393 |doi-access=free }}</ref> Some authors wrote that this has already given positive results, and tyramine content in food is now lower than it has been in the past.<ref>{{cite book |doi=10.1016/B978-0-12-386467-3.00009-1 |chapter=Selective inhibitors of monoamine oxidase type B and the "cheese effect" |title=Monoamine Oxidase and their Inhibitors |series=International Review of Neurobiology |year=2011 | vauthors = Finberg JP, Gillman K |volume=100 |pages=169–190 |pmid=21971008 |isbn=978-0-12-386467-3 }}</ref>

===In plants===
[[Mistletoe]] (toxic and not used by humans as a food, but historically used as a medicine).<ref>{{cite web |date=19 December 2005 |title=Tyramine |url=https://www.acs.org/content/acs/en/molecule-of-the-week/archive/t/tyramine.html |website=American Chemical Society |language=en}}</ref>

===In animals===
Tyramine also plays a role in animals including: In [[behavior]]al and [[motor neuron|motor]] functions in ''[[Caenorhabditis elegans]]'';<ref name="Alkema-Hunter-Ensor-Ringstad-Horvitz-2005" /> ''[[Locusta migratoria]]'' [[swarm behaviour|swarming behaviour]];<ref name="Ma-et-al-2015" /> and various nervous roles in ''[[Rhipicephalus]]'', ''[[Honey bee|Apis]]'', ''[[Migratory locust|Locusta]]'', ''[[Periplaneta]]'', ''[[Drosophila]]'', ''[[Phormia]]'', ''[[Papilio]]'', ''[[Bombyx]]'', ''[[Chilo (moth)|Chilo]]'', ''[[Heliothis]]'', ''[[Mamestra]]'', ''[[Agrotis]]'', and ''[[Anopheles]]''.<ref name="Ohta-Ozoe-2014" />

==Biological activity==
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|[[Monoamine releasing agent|Monoamine release]] of tyramine and related agents ({{Abbrlink|EC<sub>50</sub>|Half maximal effective concentration}}, nM)}}
|-
! Compound !! data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} !! data-sort-type="number" | {{abbrlink|DA|Dopamine}} !! data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} !! Ref
|-
| [[Phenethylamine]] || 10.9 || 39.5 || >10,000 || <ref name="ReithBLoughHong2015">{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug and Alcohol Dependence | volume = 147 | issue =  | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 }}</ref><ref name="Forsyth2012">{{cite web | last=Forsyth | first=Andrea N | title=Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines | website=ScholarWorks@UNO | date=22 May 2012 | url=https://scholarworks.uno.edu/td/1436/ | access-date=4 November 2024}}</ref><ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken [NJ] | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}</ref>
|-
| Tyramine || 40.6 || 119 || 2,775 || <ref name="RothmanBaumannDersch2001" /><ref name="Blough2008" />
|-
| [[Dopamine]] || 66.2 || 86.9 || >10,000 ({{Abbr|RI|Reuptake inhibitor}}) || <ref name="RothmanBaumannDersch2001" /><ref name="Blough2008" />
|-
| [[Norepinephrine]] || 164 || 869 || >10,000 || <ref name="RothmanBaumannDersch2001" /><ref name="Blough2008" />
|-
| [[Tryptamine]] || 716 || 164 || 32.6 || <ref name="BloughLandavazoDecker2014">{{cite journal | vauthors = Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB | title = Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes | journal = Psychopharmacology | volume = 231 | issue = 21 | pages = 4135–4144 | date = October 2014 | pmid = 24800892 | pmc = 4194234 | doi = 10.1007/s00213-014-3557-7 }}</ref><ref name="BloughLandavazoPartilla2014">{{cite journal | vauthors = Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, Rothman RB | title = Alpha-ethyltryptamines as dual dopamine-serotonin releasers | journal = Bioorganic & Medicinal Chemistry Letters | volume = 24 | issue = 19 | pages = 4754–4758 | date = October 2014 | pmid = 25193229 | pmc = 4211607 | doi = 10.1016/j.bmcl.2014.07.062 }}</ref>
|-
| [[Dextroamphetamine]] || 6.6–7.2 || 5.8–24.8 || 698–1,765 || <ref name="RothmanBaumannDersch2001">{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref><ref name="BaumannPartillaLehner2013">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref>
|-
| colspan="5" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. The [[bioassay|assay]]s were done in rat brain [[synaptosome]]s and human [[potency (pharmacology)|potencies]] may be different. See also [[Monoamine releasing agent#Activity profiles|Monoamine releasing agent § Activity profiles]] for a larger table with more compounds. '''Refs:'''<ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}</ref><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = https://zenodo.org/record/1235860 }}</ref>
|}

Tyramine is a [[norepinephrine–dopamine releasing agent|norepinephrine and dopamine releasing agent]] (NDRA) and indirectly acting [[sympathomimetic]].<ref name="RothmanBaumannDersch2001" /><ref name="Blough2008" /> Evidence for the presence of tyramine in the human brain has been confirmed by postmortem analysis.<ref>{{cite journal | vauthors = Philips SR, Rozdilsky B, Boulton AA | title = Evidence for the presence of m-tyramine, p-tyramine, tryptamine, and phenylethylamine in the rat brain and several areas of the human brain | journal = Biological Psychiatry | volume = 13 | issue = 1 | pages = 51–7 | date = February 1978 | pmid = 623853 }}</ref> Additionally, the possibility that tyramine acts directly as a [[neuromodulator]] was revealed by the discovery of a [[G protein-coupled receptor]] with high [[affinity (pharmacology)|affinity]] for tyramine, called the [[trace amine-associated receptor]] (TAAR1).<ref>{{cite journal | vauthors = Navarro HA, Gilmour BP, Lewin AH | title = A rapid functional assay for the human trace amine-associated receptor 1 based on the mobilization of internal calcium | journal = Journal of Biomolecular Screening | volume = 11 | issue = 6 | pages = 688–93 | date = September 2006 | pmid = 16831861 | doi = 10.1177/1087057106289891 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Liberles SD, Buck LB | title = A second class of chemosensory receptors in the olfactory epithelium | journal = Nature | volume = 442 | issue = 7103 | pages = 645–50 | date = August 2006 | pmid = 16878137 | doi = 10.1038/nature05066 | s2cid = 2864195 | bibcode = 2006Natur.442..645L }}</ref> The TAAR1 receptor is found in the [[brain]], as well as peripheral tissues, including the [[kidney]]s.<ref>{{cite journal | vauthors = Xie Z, Westmoreland SV, Miller GM | title = Modulation of monoamine transporters by common biogenic amines via trace amine-associated receptor 1 and monoamine autoreceptors in human embryonic kidney 293 cells and brain synaptosomes | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 325 | issue = 2 | pages = 629–640 | date = May 2008 | pmid = 18310473 | doi = 10.1124/jpet.107.135079 | s2cid = 178180 }}</ref> Tyramine is a [[full agonist]] of the TAAR1 in rodents and humans.<ref name="GainetdinovHoenerBerry2018">{{cite journal | vauthors = Gainetdinov RR, Hoener MC, Berry MD | title = Trace Amines and Their Receptors | journal = Pharmacol Rev | volume = 70 | issue = 3 | pages = 549–620 | date = July 2018 | pmid = 29941461 | doi = 10.1124/pr.117.015305 | url = | doi-access = free }}</ref><ref name="Human trace amines and hTAARs October 2016 review">{{cite journal | vauthors = Khan MZ, Nawaz W | title = The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system | journal = Biomedicine & Pharmacotherapy | volume = 83 | pages = 439–449 | date = October 2016 | pmid = 27424325 | doi = 10.1016/j.biopha.2016.07.002 }}</ref>

{{anchor|Effects}}

Tyramine is physiologically metabolized by [[monoamine oxidase]]s (primarily [[monoamine oxidase A|MAO-A]]), [[FMO3]], [[PNMT]], [[Dopamine beta-hydroxylase|DBH]], and [[CYP2D6]].<ref name="BRENDA FMO3 Homo sapiens">{{cite encyclopedia | title=Trimethylamine monooxygenase (Homo sapiens)| url=http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0 | encyclopedia=BRENDA | publisher=Technische Universität Braunschweig | access-date=18 September 2016 | date=July 2016 }}</ref><ref name="FMO">{{cite journal | vauthors = Krueger SK, Williams DE | title = Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism | journal = Pharmacology & Therapeutics | volume = 106 | issue = 3 | pages = 357–87 | date = June 2005 | pmid = 15922018 | pmc = 1828602 | doi = 10.1016/j.pharmthera.2005.01.001 }}<br />[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602/table/T5/ Table 5: N-containing drugs and xenobiotics oxygenated by FMO]</ref><ref name="Trace amine template 1" /><ref name="Trace amine template 2" /><ref name="CYP2D6 tyramine-dopamine metabolism" /> Human monoamine oxidase enzymes metabolize tyramine into [[4-hydroxyphenylacetaldehyde]].<ref name="HMDB 4-Hydroxyphenylacetaldehyde">{{cite web |title=4-Hydroxyphenylacetaldehyde |url=http://www.hmdb.ca/metabolites/HMDB0003767 |website=Human Metabolome Database&nbsp;– Version 4.0 |publisher=University of Alberta |access-date=8 August 2019 |date=2019-07-23}}</ref> If monoamine metabolism is compromised by the use of [[monoamine oxidase inhibitor]]s (MAOIs) and foods high in tyramine are ingested, a [[hypertensive emergency|hypertensive crisis]] can result, as tyramine also can displace stored monoamines, such as [[dopamine]], [[norepinephrine]], and [[epinephrine]], from pre-[[synaptic vesicles]]. Tyramine is considered a "[[false neurotransmitter]]", as it enters noradrenergic nerve terminals and displaces large amounts of norepinephrine, which enters the blood stream and causes vasoconstriction.

Additionally, cocaine has been found to block blood pressure rise that is originally attributed to tyramine, which is explained by the blocking of [[adrenaline]] by cocaine from reabsorption to the brain.<ref>{{cite news |id={{ProQuest|1346292101}} | vauthors = Bynum W |title=REVIEW --- Books: What Sets Your Heart Pounding |newspaper=Wall Street Journal |date=27 April 2013 |page=C.6 }}</ref>

The first signs of this effect were discovered by a British pharmacist who noticed that his wife, who at the time was on MAOI medication, had severe headaches when eating cheese.<ref>{{cite journal | vauthors = Sathyanarayana Rao TS, Yeragani VK | title = Hypertensive crisis and cheese | journal = Indian Journal of Psychiatry | volume = 51 | issue = 1 | pages = 65–6 | date = January 2009 | pmid = 19742203 | pmc = 2738414 | doi = 10.4103/0019-5545.44910 | doi-access = free }}</ref> For this reason, it is still called the "cheese reaction" or "cheese crisis", although other foods can cause the same problem.<ref>{{cite web |title=Drugs, The Straight Facts: Antidepressants |pages=30–31 | vauthors = Mitchell ES | veditors = Triggle DJ |publisher=[[Chelsea House Publishers]] |url=http://iftandcs.org/Addictions/Drugs%20The%20Straight%20Facts,%20Antidepressants.pdf |archive-url=https://web.archive.org/web/20170214224003/http://iftandcs.org/Addictions/Drugs%20The%20Straight%20Facts,%20Antidepressants.pdf |archive-date=2017-02-14 |date=2004 |access-date=2022-10-06}}</ref>

Most processed cheeses do not contain enough tyramine to cause hypertensive effects, although some aged cheeses (such as [[Stilton cheese|Stilton]]) do.<ref>{{cite journal | vauthors = Stahl SM, Felker A | title = Monoamine oxidase inhibitors: a modern guide to an unrequited class of antidepressants | journal = CNS Spectrums | volume = 13 | issue = 10 | pages = 855–870 | date = October 2008 | pmid = 18955941 | doi = 10.1017/S1092852900016965 | s2cid = 6118722 }}</ref><ref>{{cite web | url = http://web.squ.edu.om/med-lib/med_cd/e_cds/Griffith's%20Instructions%20Patients/pdf/Pg570.pdf | title = Tyramine-restricted Diet | archive-url = https://web.archive.org/web/20140513145012/http://web.squ.edu.om/med-lib/med_cd/e_cds/Griffith's%20Instructions%20Patients/pdf/Pg570.pdf | archive-date=13 May 2014 | date = 1998 | publisher = W.B. Saunders Company }}</ref>

A large dietary intake of tyramine (or a dietary intake of tyramine while taking MAO inhibitors) can cause the tyramine pressor response, which is defined as an increase in [[systolic blood pressure]] of 30 [[mmHg]] or more. The increased release of norepinephrine (noradrenaline) from neuronal cytosol or storage vesicles is thought to cause the [[vasoconstriction]] and increased heart rate and blood pressure of the pressor response. In severe cases, [[adrenergic crisis]] can occur.{{Medical citation needed|date=April 2013}} Although the mechanism is unclear, tyramine ingestion also triggers migraine attacks in sensitive individuals and can even lead to stroke.<ref>{{Cite encyclopedia|title=Tyramine | encyclopedia = Biochemistry | publisher = Encyclopedia Britannica|url=https://www.britannica.com/science/tyramine|access-date=2021-11-12 |language=en}}</ref> Vasodilation, dopamine, and circulatory factors are all implicated in the migraines. Double-blind trials suggest that the effects of tyramine on migraine may be [[adrenergic]].<ref>{{cite journal | vauthors = Ghose K, Coppen A, Carrol D | title = Intravenous tyramine response in migraine before and during treatment with indoramin | journal = British Medical Journal | volume = 1 | issue = 6070 | pages = 1191–3 | date = May 1977 | pmid = 324566 | pmc = 1606859 | doi = 10.1136/bmj.1.6070.1191 }}</ref>

Research reveals a possible link between [[migraines]] and elevated levels of tyramine. A 2007 review published in Neurological Sciences<ref>{{cite journal | vauthors = D'Andrea G, Nordera GP, Perini F, Allais G, Granella F | title = Biochemistry of neuromodulation in primary headaches: focus on anomalies of tyrosine metabolism | journal = Neurological Sciences | volume = 28 | issue = S2 | pages = S94-6 | date = May 2007 | pmid = 17508188 | doi = 10.1007/s10072-007-0758-4 | s2cid = 1548732 }}</ref> presented data showing migraine and cluster diseases are characterized by an increase of circulating neurotransmitters and [[Neuromodulation (biology)|neuromodulators]] (including tyramine, [[octopamine]], and [[synephrine]]) in the hypothalamus, amygdala, and dopaminergic system. People with migraine are over-represented among those with inadequate natural monoamine oxidase, resulting in similar problems to individuals taking MAO inhibitors. Many migraine attack triggers are high in tyramine.<ref>{{Cite news|url=http://www.headaches.org/headache-sufferers-diet/|title=Headache Sufferer's Diet {{!}} National Headache Foundation|work=National Headache Foundation|access-date=2017-04-08|language=en-US|archive-url=https://web.archive.org/web/20170702160059/http://www.headaches.org/headache-sufferers-diet|archive-date=2 July 2017}}</ref>

If one has had repeated exposure to tyramine, however, there is a decreased pressor response; tyramine is degraded to octopamine, which is subsequently packaged in synaptic vesicles with norepinephrine (noradrenaline).{{Citation needed|date=May 2014}} Therefore, after repeated tyramine exposure, these vesicles contain an increased amount of octopamine and a relatively reduced amount of norepinephrine. When these vesicles are secreted upon tyramine ingestion, there is a decreased pressor response, as less norepinephrine is secreted into the [[synapse]], and octopamine does not activate alpha or beta [[adrenergic receptors]].{{Medical citation needed|date=April 2013}}

When using a MAO inhibitor (MAOI), an intake of approximately 10 to 25&nbsp;mg of tyramine is required for a severe reaction, compared to 6 to 10&nbsp;mg for a mild reaction.<ref>{{cite journal | vauthors = McCabe BJ | title = Dietary tyramine and other pressor amines in MAOI regimens: a review | journal = Journal of the American Dietetic Association | volume = 86 | issue = 8 | pages = 1059–64 | date = August 1986 | doi = 10.1016/S0002-8223(21)04074-8 | pmid = 3525654 | s2cid = 902921 }}</ref>

Tyramine, like [[phenethylamine]], is a [[monoaminergic activity enhancer]] (MAE) of [[serotonin]], [[norepinephrine]], and [[dopamine]] in addition to its catecholamine-releasing activity.<ref name="ShimazuMiklya2004">{{cite journal | vauthors = Shimazu S, Miklya I | title = Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 28 | issue = 3 | pages = 421–427 | date = May 2004 | pmid = 15093948 | doi = 10.1016/j.pnpbp.2003.11.016 | s2cid = 37564231 }}</ref><ref name="Knoll2003">{{cite journal | vauthors = Knoll J | title = Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives | journal = Neurochem Res | volume = 28 | issue = 8 | pages = 1275–1297 | date = August 2003 | pmid = 12834268 | doi = 10.1023/a:1024224311289 | url = }}</ref><ref name="KnollMiklyaKnoll1996">{{cite journal | vauthors = Knoll J, Miklya I, Knoll B, Markó R, Rácz D | title = Phenylethylamine and tyramine are mixed-acting sympathomimetic amines in the brain | journal = Life Sci | volume = 58 | issue = 23 | pages = 2101–2114 | date = 1996 | pmid = 8649195 | doi = 10.1016/0024-3205(96)00204-4 | url = }}</ref> That is, it enhances the [[action potential]]-mediated release of these [[monoamine neurotransmitter]]s.<ref name="ShimazuMiklya2004" /><ref name="Knoll2003" /><ref name="KnollMiklyaKnoll1996" /> The compound is active as a MAE at much lower concentrations than the concentrations at which it induces the release of catecholamines.<ref name="ShimazuMiklya2004" /><ref name="Knoll2003" /><ref name="KnollMiklyaKnoll1996" /> The MAE actions of tyramine and other MAEs may be mediated by TAAR1 agonism.<ref name="HarsingKnollMiklya2022">{{cite journal | vauthors = Harsing LG, Knoll J, Miklya I | title = Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum | journal = Int J Mol Sci | volume = 23 | issue = 15 | date = August 2022 | page = 8543 | pmid = 35955676 | pmc = 9369307 | doi = 10.3390/ijms23158543 | doi-access = free | url = }}</ref><ref name="HarsingTimarMiklya2023">{{cite journal | vauthors = Harsing LG, Timar J, Miklya I | title = Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline | journal = Int J Mol Sci | volume = 24 | issue = 17 | date = August 2023 | article-number = 13334 | pmid = 37686140 | pmc = 10487936 | doi = 10.3390/ijms241713334 | doi-access = free | url = }}</ref>

==Biosynthesis==
Biochemically, tyramine is produced by the [[decarboxylation]] of [[tyrosine]] via the action of the enzyme [[tyrosine decarboxylase]].<ref>{{cite encyclopedia | url = http://www.genome.jp/kegg/pathway/map/map00350.html | title = Tyrosine metabolism - Reference pathway | encyclopedia = Kyoto Encyclopedia of Genes and Genomes (KEGG) | access-date = 3 October 2011 | archive-date = 26 July 2019 | archive-url = https://web.archive.org/web/20190726082244/http://www.genome.jp/kegg/pathway/map/map00350.html }}</ref> Tyramine can, in turn, be converted to methylated [[alkaloid]] derivatives [[N-Methyltyramine|''N''-methyltyramine]], [[hordenine|''N'',''N''-dimethyltyramine]] (hordenine), and [[candicine|''N'',''N'',''N''-trimethyltyramine]] (candicine).

<gallery class="center skin-invert-image">
File:Tyramine.svg|Tyramine
File:Methyltyramine.svg|''N''-Methyltyramine
File:Dimethyltyramine.svg|''N'',''N''-Dimethyltyramine (hordenine)
File:Candicine.svg|''N'',''N'',''N''-Trimethyltyramine (candicine)
</gallery>

In humans, tyramine is produced from tyrosine, as shown in the following diagram.{{Phenylalanine biosynthesis|align=center}}{{clear}}

==Chemistry==
In the laboratory, tyramine can be synthesized in various ways, in particular by the decarboxylation of tyrosine.<ref>{{cite journal | vauthors = Barger G | journal = J. Chem. Soc. | volume = 95 | pages = 1123–1128 | year = 1909 | doi = 10.1039/ct9099501123 | title=CXXVII.?Isolation and synthesis of p-hydroxyphenylethylamine, an active principle of ergot soluble in water| url = https://zenodo.org/record/1429723 }}</ref><ref>{{Cite journal | doi = 10.1002/hlca.192500801106 | title = Untersuchungen in der Phenylalanin-Reihe VI. Decarboxylierung des Tyrosins und des Leucins | year = 1925 | vauthors = Waser E | journal = Helvetica Chimica Acta | volume = 8 | pages = 758–773 | bibcode = 1925HChAc...8..758W }}</ref><ref>{{Cite journal | doi = 10.1021/ja01335a058 | year = 1933 | vauthors = Buck JS | journal = Journal of the American Chemical Society | volume = 55 | issue = 8 | pages = 3388–3390 | title=Reduction of Hydroxymandelonitriles. A New Synthesis of Tyramine | bibcode = 1933JAChS..55.3388B }}</ref>
[[File:Tyramine synthesis.png|class=skin-invert-image|500px|center|thumb|Tyrosine decarboxylation]]

==Society and culture==
===Legal status===
====United States====
Tyramine is a Schedule I [[controlled substance]], categorized as a [[hallucinogen]], making it illegal to buy, sell, or possess in the state of [[Florida]] without a license at any purity level or any form whatsoever. The language in the Florida [[statute]] says tyramine is illegal in "any material, compound, mixture, or preparation that contains any quantity of [tyramine] or that contains any of [its] [[Salt (chemistry)|salts]], [[isomers]], including optical, positional, or geometric isomers, and salts of isomers, if the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation."<ref name="Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL">{{Cite web|url=http://leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&URL=0800-0899/0893/0893.html|title=Statutes & Constitution :View Statutes: Online Sunshine|website=leg.state.fl.us|access-date=2019-04-03}}</ref>

This ban is likely the product of lawmakers overly eager to ban [[substituted phenethylamine]]s, which tyramine is, in the mistaken belief that ring-substituted phenethylamines are hallucinogenic drugs like the [[2C (psychedelics)|2C series]] of [[psychedelic drug|psychedelic]] substituted phenethylamines. The further banning of tyramine's [[Enantiomer|optical isomers]], [[Structural isomer#Position isomerism (regioisomerism)|positional isomers]], or [[Cis–trans isomerism|geometric isomers]], and salts of isomers where they exist, means that [[meta-tyramine]] and [[phenylethanolamine]], a substance found in every living human body, and other common, non-hallucinogenic substances are also illegal to buy, sell, or possess in Florida.<ref name="Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL"/> Given that tyramine occurs naturally in many foods and drinks (most commonly as a by-product of bacterial fermentation), e.g. wine, cheese, and chocolate, Florida's total ban on the substance may prove difficult to enforce.<ref>{{cite journal | vauthors = Suzzi G, Torriani S | title = Editorial: Biogenic amines in foods | journal = Frontiers in Microbiology | volume = 6 | page = 472 | date = 2015-05-18 | pmid = 26042107 | pmc = 4435245 | doi = 10.3389/fmicb.2015.00472 | doi-access = free }}</ref>

==Notes==
{{Reflist|group=note}}

==References==
{{Reflist|refs=

<ref name="Alkema-Hunter-Ensor-Ringstad-Horvitz-2005">{{cite journal | vauthors = Alkema MJ, Hunter-Ensor M, Ringstad N, Horvitz HR | title = Tyramine Functions Independently of Octopamine in the ''Caenorhabditis elegans'' Nervous System | journal = Neuron | volume = 46 | issue = 2 | pages = 247–60 | date = April 2005 | pmid = 15848803 | doi = 10.1016/j.neuron.2005.02.024 | publisher = [[Cell Press]] ([[Elsevier]] BV) | s2cid = 14914393 | doi-access = free }}</ref>

<ref name="Ohta-Ozoe-2014">{{cite book | vauthors = Ohta H, Ozoe Y | title=Advances in Insect Physiology | chapter=Molecular Signalling, Pharmacology, and Physiology of Octopamine and Tyramine Receptors as Potential Insect Pest Control Targets | publisher=[[Elsevier]] | year=2014 | volume=46 | isbn=978-0-12-417010-0 | doi=10.1016/b978-0-12-417010-0.00002-1 | pages=73–166 | s2cid=80723865}}</ref>

<ref name="Ma-et-al-2015">{{cite journal | vauthors = Ma Z, Guo X, Lei H, Li T, Hao S, Kang L | title = Octopamine and tyramine respectively regulate attractive and repulsive behavior in locust phase changes | journal = Scientific Reports | volume = 5 | issue = 1 | article-number = 8036 | date = January 2015 | pmid = 25623394 | pmc = 5389030 | doi = 10.1038/srep08036 | publisher = [[Nature Research|Nature]]/[[Springer Science+Business Media|Springer]] | bibcode = 2015NatSR...5.8036M | s2cid = 2056338 }}</ref>

}}

{{Neurotransmitters}}
{{Monoamine releasing agents}}
{{Monoaminergic activity enhancers}}
{{TAAR ligands}}
{{Phenethylamines}}
{{Chocolate}}

[[Category:Antihypotensive agents]]
[[Category:Migraine]]
[[Category:Monoamine oxidase inhibitors]]
[[Category:Monoaminergic activity enhancers]]
[[Category:Norepinephrine-dopamine releasing agents]]
[[Category:Peripherally selective drugs]]
[[Category:Phenethylamine alkaloids]]
[[Category:Phenethylamines]]
[[Category:TAAR1 agonists]]
[[Category:Trace amines]]
[[Category:4-Hydroxyphenyl compounds]]
[[Category:Aminoethyl compounds]]