Tyramine occurs widely in plants[5] and animals, and is metabolized by various enzymes, including monoamine oxidases. In foods, it often is produced by the decarboxylationoftyrosine during fermentationordecay. 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:[6][7]
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
Scientists more and more consider tyramine in food as an aspect of safety.[9] 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.[10] 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.[11]
Evidence for the presence of tyramine in the human brain has been confirmed by postmortem analysis.[16] Additionally, the possibility that tyramine acts directly as a neuromodulator was revealed by the discovery of a G protein-coupled receptor with high affinity for tyramine, called TAAR1.[17][18] The TAAR1 receptor is found in the brain, as well as peripheral tissues, including the kidneys.[19] Tyramine binds to TAAR1 as an agonist in humans.[20]
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.[27]
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.[28] For this reason, it is still called the "cheese reaction" or "cheese crisis", although other foods can cause the same problem.[29]
Most processed cheeses do not contain enough tyramine to cause hypertensive effects, although some aged cheeses (such as Stilton) do.[30][31]
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] Although the mechanism is unclear, tyramine ingestion also triggers migraine attacks in sensitive individuals and can even lead to stroke.[32] 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.[33]
Research reveals a possible link between migraines and elevated levels of tyramine. A 2007 review published in Neurological Sciences[34] presented data showing migraine and cluster diseases are characterized by an increase of circulating neurotransmitters and 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.[35]
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] 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]
When using a MAO inhibitor (MAOI), an intake of approximately 10 to 25 mg of tyramine is required for a severe reaction, compared to 6 to 10 mg for a mild reaction.[36]
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] 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."[41]
This ban is likely the product of lawmakers overly eager to ban substituted phenethylamines, which tyramine is, in the mistaken belief that ring-substituted phenethylamines are hallucinogenic drugs like the 2C seriesofpsychedelic substituted phenethylamines. The further banning of tyramine's optical isomers, positional isomers, or 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.[41] 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.[42]
^Synonyms and alternative names include: 4-hydroxyphenethylamine, para-tyramine, mydrial, and uteramin; the latter two names are not commonly used. The IUPAC name is 4-(2-aminoethyl)phenol.
^Finberg JP, Gillman K (2011). "Selective inhibitors of monoamine oxidase type B and the "cheese effect"". Monoamine Oxidase and their Inhibitors. International Review of Neurobiology. Vol. 100. pp. 169–190. doi:10.1016/B978-0-12-386467-3.00009-1. ISBN978-0-12-386467-3. PMID21971008.
^"Tyramine". American Chemical Society. 19 December 2005.
^Philips SR, Rozdilsky B, Boulton AA (February 1978). "Evidence for the presence of m-tyramine, p-tyramine, tryptamine, and phenylethylamine in the rat brain and several areas of the human brain". Biological Psychiatry. 13 (1): 51–7. PMID623853.
^Xie Z, Westmoreland SV, Miller GM (May 2008). "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". The Journal of Pharmacology and Experimental Therapeutics. 325 (2): 629–640. doi:10.1124/jpet.107.135079. PMID18310473. S2CID178180.
^Khan MZ, Nawaz W (October 2016). "The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system". Biomedicine & Pharmacotherapy. 83: 439–449. doi:10.1016/j.biopha.2016.07.002. PMID27424325.
^ abLindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID15860375.
^ abWang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D". European Journal of Pharmacology. 724: 211–218. doi:10.1016/j.ejphar.2013.12.025. PMID24374199.
^"4-Hydroxyphenylacetaldehyde". Human Metabolome Database – Version 4.0. University of Alberta. 23 July 2019. Retrieved 8 August 2019.
^Bynum W (27 April 2013). "REVIEW --- Books: What Sets Your Heart Pounding". Wall Street Journal. p. C.6. ProQuest1346292101.
^Stahl SM, Felker A (October 2008). "Monoamine oxidase inhibitors: a modern guide to an unrequited class of antidepressants". CNS Spectrums. 13 (10): 855–870. doi:10.1017/S1092852900016965. PMID18955941. S2CID6118722.
^McCabe BJ (August 1986). "Dietary tyramine and other pressor amines in MAOI regimens: a review". Journal of the American Dietetic Association. 86 (8): 1059–64. doi:10.1016/S0002-8223(21)04074-8. PMID3525654. S2CID902921.
^Waser E (1925). "Untersuchungen in der Phenylalanin-Reihe VI. Decarboxylierung des Tyrosins und des Leucins". Helvetica Chimica Acta. 8: 758–773. doi:10.1002/hlca.192500801106.
^Buck JS (1933). "Reduction of Hydroxymandelonitriles. A New Synthesis of Tyramine". Journal of the American Chemical Society. 55 (8): 3388–3390. doi:10.1021/ja01335a058.
‡ References for synthetic TAAR1 agonists can be found at TAAR1 or in the associated compound articles. For TAAR2 and TAAR5 agonists and inverse agonists, see TAAR for references.
