Biogenic amines are organic nitrogen compounds of small molecular weight. Biogenic amines are formed because of decarboxylation of amino acids during the conversion of carbohydrate units of lactic acid and organic compounds by microorganisms that enable the ripening of foods (fermentation). When taken in high amounts, they cause food intoxication. Toxic amounts of biogenic amines are produced during processing, preparation and storage of protein-rich plant and animal products. Natural biogenic amines in animal and human cells are formed by decarboxylation of amino acids or amination and transamination of aldehydes and ketones. They are especially molecules having aromatic and heterocyclic structures. Five of the natural biogenic amines (dopamine, norepinephrine, epinephrine, histamine and serotonin) play important roles in the body as neurotransmitters 678. However, they can cause harmful effects when taken with high amounts of food.

A suitable medium is required for decarboxylation reactions during the formation of biogenic amines. This medium is provided by the processes of preparation of foodstuffs, such as the presence of free amino acids, microbial contamination and heat treatment. Biogenic amines (such as adrenaline, histamine, tyramine, and serotonin) involved in normal physiological processes should be evaluated differently from toxic biological amines 691011. All catechol-derived biogenic amines are composed of tyrosine amino acid that is a common precursor. Biogenic amines can be detected very precisely by GS-MS or HPLC 12.

Dopamine, an important biogenic amine, responsible for the sense of motivation and reward, is synthesized by decarboxylation of 3,4-dihydroxyphenylalanine (Figure 1). Dopamine is commonly found in the corpus striatum, which plays an important role in the coordination of the body's motor movements 1314. This region is thought to be degenerate in Alzheimer's disease. Therefore, in order to compensate for the reduced dopamine, L-dopa is given which can cross the blood-brain barrier in treatment. However, the state of the decarboxylase enzymes that converts dopamine molecules and the peripheral catabolism of L-dopa should not be ignored. As is known, as soon as L-dopa is taken, it is rapidly catabolized in the intestine and peripheral tissues. Therefore, L-dopa is given together with carbidopa, a dopamine decarboxylase inhibitor that does not cross the blood-brain barrier, and selegiline, a monoamine oxidase (MAO) inhibitor 1516. However, hydrazine, a degradation product of carbidopa, is genotoxic and possibly carcinogenic. Dopamine is also used in shock treatment because it enlarges the renal arteries and activates β-adrenergic receptors in the heart and increases cardiac output.

In a study investigating renal effects of biogenic amines; It has been found that dopamine and 5-hydroxytryptamine are converted to each other by the aromatic L-amino acid decarboxylase enzyme in the renal tubular cells 17. L-dopa and dopamine affect the transfer of Na⁺ outside the cell and K⁺ inside the cell by reversible inhibition of Na⁺-K⁺ ATPase. These vasoactive amines act on dopaminergic receptors in the renal and coronary vessels, increasing blood flow without altering blood pressure. Therefore, they accelerate glomerular filtration while increasing renal blood flow. It also inhibits aldosterone synthesis and Na-K ATPase pumps, resulting in natriuresis 1819. This makes it difficult to keep the water in the intravascular area. This also suggests that, biogenic amines taken through food can lead to blood pressure changes and renal effects, through intrarenal transformations. This will cause more serious health problems in patients with impaired anti-toxic metabolism, hypotensive/hypertensive patients, and those with heart or renal disease.

Dopamine levels are associated with some urological diseases. For example, bupropion, a norepinephrine-dopamine reuptake inhibitor (NDRI), was found to reduce sperm motility in rats when taken at a dose of ≥30 mg/kg. However, it has been reported that methylphenidate, an NDRI, increases the rate of sperm with abnormal tail morphology in rats, increases the number of spermatogonia and sperm, and reduces the number of round spermatids. In addition, sibutramine has been reported to shorten the passage of sperm from the epididymis and reduce the total number of sperm in the epididymis, in rats 20. Chen G. et al. demonstrated that disruption of the Dopamine-2 receptor pathway in the basolateral amygdala in rats may contribute to the development of non-organic erectile dysfunction (ED) and that dopamine-2 receptor agonists may rehabilitate ED in rat models with non-organic ED 21.

Another biogenic amine, norepinephrine, is synthesized from dopamine by the dopamine β-hydroxylase enzyme found in the vesicles. From here, it is transported to the adrenergic nerve terminals. The most prominent class of neurons expressing norepinephrine are sympathetic ganglion cells 131422. Norepinephrine is also an important transmitter of locus coeruleus, a brain stem core associated with sleep and alertness, attention and feeding behavior.As shown in Figure 2, norepinephrine is a neurotransmitter acting on smooth muscle in postganglionic sympathetic neurons, causing contraction or relaxation depending on the type of receptors. Dopamine is a neurotransmitter that modulates cholinergic transmission in autonomic ganglia. It also inhibits Na⁺ and H₂O reabsorption in the kidneys and causes renal vasodilatation 232425. Epinephrine and norepinephrine are neurohumoral agents that are released into the bloodstream by the adrenal medulla. The amount of epinephrine released is quite high compared to norepinephrine. All these biogenic amines are essential for the physiological functions of the body. However, when taken in high amounts, they cause serious problems.

Excess norepinephrine in various tissues has been associated with some diseases. For example, In a study by Stein et al., It was reported that norepinephrine increased in the urine of patients with interstitial cystitis 26. Diederichs et al. have reported that intracavernous administration of norepinephrine (in a dose-dependent manner) reduced penile erection due to cavernous nerve. Sympathetic stimulation reduces or completely eliminates penile erection induced by acetylcholine or vasoactive intestinal polypeptide. It has been concluded that norepinephrine is an important neurotransmitter in the control of penile detumescence 27.

Epinephrine is present in the brain at lower levels than other catecholamines. It is also called adrenaline. Phenylethanolamine-N methyl transferase, which synthesizes epinephrine, is present only in neurons that secrete epinephrine. The function of epinephrine-containing neurons in the central nervous system is not fully understood. There are two main enzymes involved in the catabolism of catecholamines, mitochondrial monoamine oxidase (MAO) and cytoplasmic catechol O methyl transferase (COMT) in neurons and glial cells. Inhibitors of these enzymes are used as antidepressants in psychiatry clinics 222829. Especially, it is produced by the adrenal medulla, which is a postsynaptic ganglion organ, reaching the peripheral tissues through circulation. It is produced by the adrenal medulla, which is a postsynaptic ganglion, and reaches to peripheral tissues through circulation.

Epinephrine has many vital effects and has place in treatments. For example, it is still used successfully in the treatment of emergency priapism cases 30. In addition, intravesical administration of epinephrine has been inhibited hemorrhage and inflammation in bladder in a rat model that has cyclophosphamide-induced hemorrhagic cystitis 31.

Histamine is a biogenic amine synthesized from histidine by histidine decarboxylase. Histamine methyltransferase and MAO are involved in its catabolism. Histamine and histidine decarboxylase are found in neurons in the hypothalamus and histamine receptors are intensely found in neurons in almost all regions of the brain and spinal cord. Histamine mediates arousal and attention in the central nervous system, as does acetylcholine and norepinephrine 3233. In peripheral tissues, histamine is released from mast cells in response to tissue damage and allergic reactions. Histamine is also effective in modulating bladder contraction. Stromberga et al. reported that the stimulation of H1 histaminic receptors caused contractions in both the lamina propria and detrusor tissue of the urinary bladder. Activation of H2 histaminic receptors is only prevents H1 receptor-mediated contractions in the lamina propria, not in detrusor tissue. Based on these results, H1 and H2 receptors may be potential targets in the future, in the treatment of overactive bladder and other bladder contraction disorders 34.

Serotonin (5-hydroxytryptamine) is synthesized from tryptophan, an essential amino acid (Figure 3). Tryptophan is taken into the neurons by a membrane transporter and is initially hydroxylated by the enzyme tryptophan-5-hydroxylase. This stage is the control step of serotonin synthesis. Then, this hydroxylated form is decarboxylated and the synthesis of serotonin is completed. Serotonin is found intensely in neurons in the pons and brain stem. It has an important role in sleeping and staying awake. Its effects in the synaptic range are terminated by withdrawing from the intersynaptic junction, like other biogenic amines. Many antipsychotic drugs used in the treatment of depression and anxiety are thought to have serotonergic effects 223536. Mitochondrial MAO has an important role in its catabolism. The NE and 5-HT monoaminergic systems play an important role in controlling a wide range of behavioral and physiological processes, including sleep, cognition, and mood. Homeostasis of central NE and 5-HT neurons is achieved by signal controls of the NE and 5-HT autoreceptors. In addition to its neuropsychiatric effects, serotonin has many associations with other systems and diseases. For example, Siddiqui et al. have reported that blockade of 5-Hydroxytryptamine 1A (5HT1A) receptors and, to a greater extent, 5-Hydroxytryptamine 1B (5HT1B) receptors significantly inhibits bladder cancer cell growth and may be used in the treatment of bladder cancer 37.