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 neurotransmitter 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. The existence of a receptor with high affinity for tyramine supports the hypothesis that tyramine may also act directly to affect blood pressure regulation.[medical citation needed]
Tyramine is physiologically metabolized by MAOA. In humans, 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 can also displace stored monoamines, such as dopamine, norepinephrine and epinephrine, from pre-synaptic vesicles. The first signs of this were discovered by a neurologist who noticed his wife, who at the time was on MAOI medication, had severe headaches when eating cheese. For this reason, the crisis 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 displacement of norepinephrine (noradrenaline) from neuronal storage vesicles by acute tyramine ingestion 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]
However, if one has had repeated exposure to tyramine, there is a decreased pressor response; tyramine is degraded to octopamine, which is subsequently packaged in synaptic vesicles with norepinephrine (noradrenaline). 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), the 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.[medical citation needed]
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 characterised by an increase of circulating neurotransmitters and neuromodulators (including tyramine, octopamine and synephrine) in the hypothalamus, amygdala and dopaminergic system.