Tyramine

Tyramine (/ˈtaɪrəmiːn/ TY-rə-meen) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs). Tyramine occurs widely in plants and animals, and is metabolized by various enzymes, including monoamine oxidases. In foods, it often is produced by the decarboxylation of tyrosine during fermentation or decay. Foods containing considerable amounts of tyramine include: Evidence for the presence of tyramine in the human brain has been confirmed by postmortem analysis. 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. The TAAR1 receptor is found in the brain, as well as peripheral tissues, including the kidneys. Tyramine binds to both TAAR1 and TAAR2 as an agonist in humans. Tyramine is physiologically metabolized by monoamine oxidases (primarily MAO-A), FMO3, PNMT, DBH, and CYP2D6. Human monoamine oxidase enzymes metabolize tyramine into 4-hydroxyphenylacetaldehyde. If monoamine metabolism is compromised by the use of monoamine oxidase inhibitors (MAOIs) and foods high in tyramine are ingested, a hypertensive crisis can result, as tyramine also can displace stored monoamines, such as dopamine, norepinephrine, and epinephrine, from pre-synaptic vesicles. 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. For this reason, it is still called the 'cheese effect' or 'cheese crisis,' though other foods can cause the same problem.:30–31 Most processed cheeses do not contain enough tyramine to cause hypertensive effects, although some aged cheeses (such as Stilton) do. 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. Although the mechanism is unclear, tyramine ingestion also triggers migraines in sensitive individuals. Vasodilation, dopamine, and circulatory factors are all implicated in migraine. Double-blind trials suggest that the effects of tyramine on migraines may be adrenergic. Research reveals a possible link between migraine and elevated levels of tyramine. A 2007 review published in Neurological Sciences presented data showing migraine and cluster headaches are characterized by an increase of circulating neurotransmitters and neuromodulators (including tyramine, octopamine and synephrine) in the hypothalamus, amygdala and dopaminergic system. Migraineurs are over-represented among those with inadequate natural monoamine oxidase, resulting in similar problems to individuals taking MAO inhibitors. Many migraine triggers are high in tyramine.