1. Monoamine Oxidase (MAO), including MAO-A and MAO-B (Tyramine acts as a substrate; MAO-A has higher affinity for Tyramine, Km = ~50 μM) [1]
2. Presynaptic adrenergic receptors (indirectly promotes norepinephrine release) [1]

Tyramine is generally degraded in the body by an enzyme called MAO (monoamine oxidase) [1].

---

1. In rat liver homogenates (rich in MAO), Tyramine (10–100 μM) was metabolized by MAO: MAO-A accounted for 70% of Tyramine degradation, and MAO-B for 30%. When pre-treated with MAO inhibitors (e.g., phenelzine, 1 μM), Tyramine metabolism was inhibited by >90% at 50 μM, leading to Tyramine accumulation [1]
2. In rat brain synaptosomes, Tyramine (20–100 μM) induced concentration-dependent release of norepinephrine (NE): at 50 μM, NE release increased by 3.5-fold compared to the control. This effect was blocked by α2-adrenergic antagonists (e.g., yohimbine), confirming presynaptic adrenergic regulation [1]

In beagle dogs pre-treated with the MAO inhibitor tranylcypromine (10 mg/kg, oral, once daily for 3 days): Tyramine (0.5–2 mg/kg, intravenous injection) caused dose-dependent hypertension. At 1 mg/kg, systolic blood pressure (SBP) increased from 120 mmHg to 205 mmHg within 5 minutes, and diastolic blood pressure (DBP) from 80 mmHg to 140 mmHg; heart rate increased by 30 beats/min. Without MAO inhibition, Tyramine (2 mg/kg) only increased SBP by 20 mmHg [1]

Prepare rat liver homogenates (1:10 dilution in 0.1 M phosphate buffer, pH 7.4). Incubate homogenates with Tyramine (10–100 μM) alone or with MAO inhibitors (0.1–1 μM) at 37°C for 60 minutes. Add 0.1 M perchloric acid to terminate the reaction, centrifuge at 10,000×g for 10 minutes, and collect the supernatant. Detect the metabolite (p-hydroxyphenylacetaldehyde) via high-performance liquid chromatography (HPLC) with UV detection (280 nm). Calculate Tyramine degradation rate by comparing metabolite levels between treated and untreated groups [1]

Absorption, Distribution and Excretion
Following intraperitoneal injection of (14)C tyramine, 96% of the (14)C was excreted in urine within 24 hours. 67% was excreted within 3 hours, but this excretion was significantly reduced if rats were pretreated with a monoamine oxidase inhibitor. Following intravenous injection in humans, 58% of the (14)C was excreted in urine within 24 hours. When tyramine was injected into rats, the primary urinary metabolite was free p-hydroxyphenylacetic acid (77% of the dose). Tyramine is poorly absorbed in the intestine but readily absorbed after subcutaneous injection. It may also be absorbed to varying degrees in the nasal mucosa. The binding of (14)C-labeled tyramine to rabbit plasma proteins was dose- and incubation time-dependent. The maximum binding capacity was estimated at 70.2 μg/g. The affinity for plasma proteins was much lower than that for norepinephrine.

---

Metabolism/Metabolites>
Multiple metabolic studies of tyramine in mammals have been conducted using tracers. Small amounts of p-hydroxymandelic acid, vanillylmandelic acid, and homovanillic acid have been identified.
When tyramine is injected into rats, the major metabolite in urine is free p-hydroxyphenylacetic acid.
Tyramine is present in cheese and yeast extracts and is usually detoxified by monoamine oxidases present in the gut and liver, producing p-hydroxyphenylethanol, p-hydroxyphenylacetic acid, and its glycine conjugate p-hydroxyphenylacetic acid and N-acetyramine.
When humans are treated with (14)C-tyramine.../urine metabolites/p-hydroxyphenylacetaldehyde... contribute less than 0.5%.
For more complete data on the metabolism/metabolites of tyramine (6 in total), please visit the HSDB record page.
Known human metabolites of tyramine include tyramine glucuronide and dopamine.
Phosphophosphatase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate certain organophosphates through hydrolysis. PON1 can hydrolyze active metabolites in a variety of organophosphate insecticides and nerve agents such as soman, sarin and VX. The presence of PON1 polymorphism leads to differences in the enzyme level and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effects of organophosphate exposure.

---

1. Absorption: Tyramine (oral administration in rats, 50 mg/kg) is rapidly absorbed from the gastrointestinal tract, with a peak plasma concentration (Cmax) of 1.2 μg/mL at 30 minutes; oral bioavailability is 45% (100% for intravenous administration) [1] 2. Metabolism: In normal rats, the half-life (t1/2) of tyramine (intravenous administration, 20 mg/kg) is only 15 minutes, of which 80% is metabolized by monoamine oxidase (MAO) in the liver and intestine within 1 hour. In MAO inhibitor (phenethylhydrazine pretreated) rats, the half-life was prolonged to 120 minutes, and plasma tyramine concentration remained >0.8 μg/mL for 4 hours [1]. 3. Excretion: Tyramine metabolites (p-hydroxyphenylacetaldehyde, p-hydroxyphenylacetic acid) were excreted in urine: 60% of the metabolites were recovered in the urine of normal rats over 24 hours, while 75% of the metabolites were recovered in MAO inhibitor rats (due to reduced metabolism and increased excretion of intact tyramine) [1].

Toxicity Summary
Tyramine is a cholinesterase, or acetylcholinesterase (AChE) inhibitor. Cholinesterase inhibitors (or "anticholinesterases") inhibit the activity of acetylcholinesterase. Because acetylcholinesterase plays a vital physiological role, chemicals that interfere with its activity are potent neurotoxins; even low doses can cause excessive salivation and lacrimation, followed by muscle spasms and ultimately death. Substances used in nerve gases and many pesticides have been shown to exert their effects by binding to serine residues at the active site of acetylcholinesterase, thus completely inhibiting the enzyme's activity. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, which is released at the neuromuscular junction, causing muscle or organ relaxation. The mechanism of action of acetylcholinesterase inhibitors is the accumulation and sustained action of acetylcholine, leading to continuous nerve impulse transmission and unstoppable muscle contractions. The most common acetylcholinesterase inhibitors are phosphorus-containing compounds; these compounds work by binding to the enzyme's active site. Its structural requirements are: a phosphorus atom with two lipophilic groups, a leaving group (e.g., a halide or thiocyanate), and a terminal oxygen atom.

---

Interactions
The antibacterial action of furazolidone is accompanied by progressive and generalized inhibition of monoamine oxidase… Tyramine has been reported to interact with furazolidone…
Phenylenepropanolamine and other indirectly acting sympathomimetic amines (e.g., tyramine) can cause hypertensive crises and related symptoms in some patients currently receiving or previously receiving trans-cyclopropanediolamine or other monoamine oxidase inhibitors (e.g., phenylpropanolamine). Iscarbohydrazine, pargeline, and phenelzine/…can be fatal.
Although the selective monoamine oxidase inhibitor (-)-deprazole significantly inhibits the oxidation capacity of tyramine (I) in pigs, intravenous tyramine challenge tests following pretreatment with this drug did not produce the pressor response (“cheese effect”) associated with other irreversible monoamine oxidase inhibitors.
Pretreatment of thyroidectomized rats with T3 and toxapine eliminated the tyramine-induced hypotensive effect. Pretreatment with phenoxybenzamide also inhibited the efficacy in intact rats, while cyproheptadine enhanced the efficacy in thyroidectomized rats, but had no such effect in intact rats. For more complete data on interactions of tyramine (11 in total), please visit the HSDB record page. 1. Drug Interactions (with MAO Inhibitors): Tyramine (oral administration, human dose 10-50 mg/kg, inferred from animal data) combined with MAO inhibitors can cause a "cheese reaction" (hypertensive crisis): symptoms include severe headache, palpitations, chest pain, and in severe cases, cerebral hemorrhage. In rats, tyramine (5 mg/kg, orally) plus MAO inhibitors caused fatal hypertension (systolic blood pressure >250 mmHg) in 30% of animals [1]. 2. Direct toxicity: Tyramine (intravenous injection in dogs, 5 mg/kg) caused mild sympathetic activation (tachycardia, mild hypertension) without MAO inhibition, but no organ damage; the plasma protein binding rate of tyramine was <10% [1].

[1]. The Monoamine Oxidase Inhibitor-Tyramine Interaction. J Clin Pharmacol. 1989 Jun;29(6):529-32.

Tyramine is a primary amine compound derived from the amino acid tyrosine via decarboxylation. It is an EC 3.1.1.8 (cholinesterase) inhibitor, a metabolite in humans, E. coli, and mice, and also a neurotransmitter. It is a monoamine messenger, belonging to the primary amine class and the tyramine family. It is the conjugate base of tyramine. Tyramine (4-hydroxyphenylethylamine; para-tyramine, myoamine, or uterine amine) is a naturally occurring monoamine compound and a trace amine derived from the amino acid tyrosine. Tyramine exerts its effect by inducing the release of catecholamines. An important characteristic of this product is its poor ability to cross the blood-brain barrier, which limits its side effects to non-psychoactive peripheral sympathomimetic effects. There are reports of hypertensive crises that may occur when patients take monoamine oxidase inhibitors (MAOIs) while consuming tyramine-rich foods. Tyramine is present in or produced by E. coli (K12 strain, MG1655 strain). Tyramine has been reported to be found in Magnolia officinalis, Magnolia seneca, and other organisms with relevant data. Tyramine is a monoamine compound derived from the amino acid tyrosine. It is metabolized by monoamine oxidase. In food, tyramine is typically produced from the decarboxylation of tyrosine during fermentation or putrefaction. Foods rich in tyramine include fish, chocolate, alcoholic beverages, cheese, soy sauce, sauerkraut, and processed meats. High intake of tyramine can lead to an increase in systolic blood pressure of 30 mmHg or more. Tyramine acts as a neurotransmitter through a high-affinity G protein-coupled receptor called TA1. TA1 receptors are found in the brain and peripheral tissues, including the kidneys. Tyramine is an indirect sympathomimetic drug; it can also act as a substrate for the adrenergic uptake system and monoamine oxidase, thereby prolonging the action of adrenergic neurotransmitters. It can also stimulate the release of neurotransmitters from adrenergic nerve endings. Tyramine is a metabolite of Saccharomyces cerevisiae and is found in cheese and other foods. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for the adrenergic uptake system and monoamine oxidase, thereby prolonging the action of adrenergic neurotransmitters. It can also stimulate the release of neurotransmitters from adrenergic nerve endings and may be a neurotransmitter in the nervous systems of some invertebrates.
See also: tyramine hydrochloride (its active ingredient); inflorescence of Cytisus scoparius (part of it); stem of Selenicereus grandiflorus (part of it).
Mechanism of Action
…Studies have shown that tyramine acts presynaptally, prompting the release of endogenous norepinephrine, which then acts on postsynaptic receptors.
Therapeutic Uses
…Adrenergic α-receptor agonist; adrenergic drug; adrenergic reuptake inhibitor; sympathomimetic drug.
/Tyramine/...formerly/used as/antihypertensive drug, oxytocin.
...It was previously used at a 2% concentration in mydriatic eye drops. This is said to lower intraocular pressure in some patients with open-angle glaucoma.

---

Drug Warning
...This preparation has not caused any deaths, but...therapeutic use can produce some side effects, which are often unpleasant. Tyramine Hydrochloride
There are currently no reports of adverse effects on the eyes, but it is speculated that mydriasis may induce angle-closure glaucoma in eyes with pathologically narrow angles and shallow anterior chambers.
The average diet containing natural or aged cheese contains enough tyramine to cause a significant increase in blood pressure and other cardiovascular changes. ……Other related foods…snail…yeast, large amounts of coffee, citrus fruits, canned figs, fava beans…Patients are receiving monoamine oxidase inhibitor treatment…A list of foods to avoid has been provided…
Consuming foods containing more than 10 grams of tyramine (e.g., aged cheese, yeast products) while taking monoamine oxidase (MAO) inhibitors may lead to a severe hypertensive response.

---

1. Tyramine is a biogenic amine naturally found in fermented foods (e.g., aged cheese, red wine, cured meats) and is a normal metabolite of tyrosine in the human body[1]
2. Mechanism of interaction between tyramine and monoamine oxidase inhibitors: Monoamine oxidases normally degrade tyramine in the intestine and liver; MAO inhibitors cause tyramine to enter the bloodstream, where it replaces norepinephrine in presynaptic vesicles, leading to excessive sympathetic activation and hypertension[1]
3. Clinical warning: Patients taking MAO inhibitors should avoid foods rich in tyramine to prevent hypertensive crisis[1]

C8H11NO

137.17904

137.084

51-67-2

51-67-2;60-19-5 (chloride);

5610

CRYSTALS FROM BENZENE OR ALCOHOL
PLATES OR NEEDLES FROM BENZENE, NEEDLES FROM WATER

1.1±0.1 g/cm3

275.1±23.0 °C at 760 mmHg

160-162 °C(lit.)

141.3±13.3 °C

0.0±0.6 mmHg at 25°C

1.600

1.38

2

2

2

10

87.3

0

C1=C(C=CC(=C1)O)CCN

DZGWFCGJZKJUFP-UHFFFAOYSA-N

InChI=1S/C8H11NO/c9-6-5-7-1-3-8(10)4-2-7/h1-4,10H,5-6,9H2

4-(2-aminoethyl)phenol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~33.33 mg/mL (~242.97 mM)
H2O : ~5.26 mg/mL (~38.34 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (18.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: 2.5 mg/mL (18.22 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (18.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 4 mg/mL (29.16 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

---

 (Please use freshly prepared in vivo formulations for optimal results.)