Tyramine octopamine

Biogenic amines are of great interest to researchers because of their potential roles in several psychiatric and neurological disorders. They include dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT, serotonin), histamine, and trace amines such as 2-phenylethylamine (PEA), tyramine, octopamine, phenylethanolamine, and tryptamine (Coutts and Baker, 1982). Although GC assays for DA, NA, and 5-HT are available, HPLC analysis with electrochemical detection has for many years now been the method of choice for analysis of these neurotransmitter amines. 

Minor metabolites that accumulate because of the alternate pathways utilized in phenylketonuria may normally serve either physiological or pharmacological roles in the nervous system. To aggravate the deficiency of tyrosine created by shunting into these minor pathways in PKU, phenylalanine inhibits tyrosine transport across biological membranes. In turn, this curtails the source of neuroactive tyrosine derivatives that can be synthesized, including tyramine, octopamine, and the catecholamines. One can speculate that such deficiencies could interfere with neurotransmitter action. 

Dopamine was produced by incubating liver microsomes of rabbits with p- and m-tyramine, noradrenaline, and normetanephrine by incubation with w-octopamine, and adrenaline by incubation with p- and w-methyloctop-amine/" The injection of labelled tyramine as well as of labelled octopamine in the intact animal (rat) caused the appearance of labelled noradrenaline and normetanephrine in the urine/ As tyramine is also hydroxylated to octopamine, it is possible that the production of noradrenaline from tyramine not only takes place via its conversion to dopamine, but also via its conversion to octopamine. The possibility that octopamine is produced by the hydroxylation of tyrosine to hydroxyphenylserine with ensuing decarboxylation is under discussion. The production of noradrenaline from 3,4-dihydroxyphenylserine, 192-201) amino-acid so far not discovered in the mammal could be demonstrated both in organ extracts and in intact animals. Finally, a transamination of 3-hydroxy- or 3,4-dihydroxyphenylpyruvate to the corresponding amino-acids (m-tyrosin, dopa), and their decarboxylation to m-tyramine and dopamine was observed in intact animals (cats). For the time being it is impossible to determine the importance of the means of formation of catecholamines which have been referred to here. Of the above-mentioned precursor substances, p- and m-tyramine,( octopamine, ... 

Two important pathways for catecholamine metaboHsm are 0-methylation by COMT, which is cytoplasmicaHy localized, and oxidative deamination by the mitochondrial localized enzyme MAO. There are large amounts of MAO in tissues such as the fiver and the heart which are responsible for the removal of most of the circulating monoamine, including some taken in from the diet. Tyramine is found in high concentrations in certain foods such as cheese, and in wine. Normally, this tyramine is deaminated in the fiver. However, if MAO is inhibited, the tyramine may then be converted into octopamine [104-14-37] which may indirecdy cause release of NE from nerve terminals to cause hypertensive crisis. Thus MAO, which is relatively nonspecific, plays an important role in the detoxification of pharmacologically active amines ingested from the diet. 

Trace amines are a family of endogenous monoamine compounds including (3-phenylethylamine (PEA), p-tyramine (TYR), tryptamine (TRP) and octopamine (OCT). The trace amines share close structural similarity with the well known classical monoamine neurotransmitters such as dopamine (DA), norepinephrine (NE) and serotonin (5-HT). As their name suggests, trace amines occur in comparably much lower abundance than monoamine neurotransmitters. For historical reasons, other endogenous amine compounds which might share some structural similarities with PEA, TYR, TRP or OCT are not referred to as trace amines. 

Trace Amines. Figure 1 The main routes of trace amine metabolism. The trace amines (3-phenylethylamine (PEA), p-tyramine (TYR), octopamine (OCT) and tryptamine (TRP), highlighted by white shading, are each generated from their respective precursor amino acids by decarboxylation. They are rapidly metabolized by monoamine oxidase (MAO) to the pharmacologically inactive carboxylic acids. To a limited extent trace amines are also A/-methylated to the corresponding secondary amines which are believed to be pharmacologically active. Abbreviations AADC, aromatic amino acid decarboxylase DBH, dopamine b-hydroxylase NMT, nonspecific A/-methyltransferase PNMT, phenylethanolamine A/-methyltransferase TH, tyrosine hydroxylase. 

Tyramine is produced by decarboxylation of tyrosine and is present in the CNS in higher (threefold) concentrations than m-tyramine, the hydroxylated derivative of phenylethylamine. In the periphery / -tyramine is easily hydroxylated to octopamine, which has some direct effects on ai adrenoceptors, unlike tyramine which functions by releasing NA. When tested on central neurons tyramine always produces the same effects as NA but they are slower and less marked, implying an indirect action. By contrast octopamine often produces the opposite effect to NA and it is probable that octopamine may have a functional role in the invertebrate CNS where it is found in higher concentrations (5pg/g) than in the mammalian brain (0.5ng/g). Neither tyramine nor octopamine have distinct behavioural effects, unlike phenylethylamine,... 

A direct effect of vasoactive amines on the organism which are not degraded in GI tracts due to the lack of mono- and diaminooxidase (MAO and DAO) or their blockade by medicines or alcohol. This group of amines includes tyramine (in Cheddar, emmental, roquefort cheeses, pickled fish, and walnuts), phenylethylamine (in chocolate), serotonin (in bananas), octopamine (in lemons), and histamine (in fermented foods, e.g., blue cheeses, but also in strawberries, tomatoes, wines, and in mackerel that have not been stored properly [scombrotoxin illness]). 

On comparing the activities of the five compounds for which numerical estimates are available in all three assays (synephrine, octopamine, phenylethanolamine, norepinephrine and tyramine) the rank orders of potency in the three systems are Crayfish, 1,2,3t4,5 Cockroach, 2,1,3,4,5 Locust 1,2,3t5,4. This indicates a basic similarity in the responses of these preparations. In each case it was found that ring hydroxylation of the phenylethylamine nucleus was not essential for activity, although p-hydroxylation does yield the best activity. This is particularly evident in the crayfish study where a-MAMBA (a-methylaminomethyl benzyl alcohol), the analog of synephrine which lacks ring substitution, was one of the most active compounds tested, and 3-phenylethanolamine, the corresponding analog of OA, is almost as active as OA. The base compound for this series, phenylethylamine, also shows appreciable activity, but only in the crayfish assay. 

One pharmacological theory of the mechanism underlying postural hypotension is the false-transmitter theory. Tyramine may be metabolized to an inactive metabolite (octopamine) that partially fills the NE storage vesicles with a false (inactive) transmitter, but definitive proof is lacking. 

Biosynthesis of catecholamines. The rate-limiting step, conversion of tyrosine to dopa, can be inhibited by metyrosine (K-methyltyrosine). The alternative pathway shown by the dashed arrows has not been found to be of physiologic significance in humans. However, tyramine and octopamine may accumulate in patients treated with monoamine oxidase inhibitors. 

Fales and Pisano (30) were the first to describe the gas chromatographic analysis of amphetamine. They used 4% SE-30 in a silanized glass column and an argon ionization detector for the separation of (3-phenethylamine, amphetamine, norephedrine, eph drine, histamine, tyramine, dimethyltriptamine, tryptamine, 5-methoxytryptamine, benzylamine, N-methylbenzylamine, octopamine, synephrine, normetanephrine, serotonin, N-acetyltryptamine, find melatonin. The method was also used for the analysis of amphetamine extracted from urine. 

Hernandez-Jover et al. (72) derived an improved analytical method from the HPLC procedure setup they developed in 1995 (73) for the determination of BAs in fish. The method consists of the extensive extraction with HC104, ion-pair (with sodium octanesulfonate) RP-HPLC separation, postcolumn derivatization with PA/ME, and spectrofluorimetric detection. Determination limits were up to 1.5 mg/kg. In particular, His, Tyr, Phe, Ser (serotonine), Cre (creatinine), Try, Oct (octopamine), Dop (dopamine), Cad, Put, Agm (agmatine), Spm, and Spd were studied in pork and beef meat, fresh, cooked, or ripened. Tyramine, His, Put, Cad, and Try levels were... 

Robb S, Cheek TR, Hannan FL, Hall LM, Midgley JM, Evans PD. Agonist-specific coupling of a cloned Drosophila octopamine/tyramine receptor to multiple second messenger systems. EMBO J 1994 13 1325-1330. 

The most abundant alkaloid in Coryphantha macromeris, normacromerine, has been shown to originate from tyrosine (330). Tyramine and JV-methyltyramine are efficiently incorporated into normacromerine while octopamine and dopamine are poor precursors. Norepinephrine, epinephrine, normetanephrine, and meta-nephrine have all been shown to be biosynthetically incorporated into normacromerine, and they have also been shown to be naturally occurring trace intermediates in this cactus species (331, 334). Normacromerine is only slowly converted to macromerine in C. macromeris (332). The results indicate that alternative pathways to normacromerine exist precise conclusions regarding the biosynthesis of normacromerine must await further studies. 

The action of tyramine on nerve receptors is mainly indirect by release of norepinephrine and dopamine from neuronal storage sites (363, 384). Tyramine and its /3-oxidized counterpart octopamine have been referred to as false neurotransmitters because these compounds can be taken up, stored, and released from nerve endings in a way similar to those of the principal neurotransmitters norepinephrine and dopamine (385). Octopamine was first discovered in salivary glands of octopods (386). The compound is widely distributed in the animal kingdom and is present in high amounts in the nervous system of several species of invertebrates such as molluscs and arthropods, where it acts as a specific transmitter substance (387). Octopamine may also play a role in the regulation of adrenergic neurotransmission in mammals (387). Administration of octopamine to intact animals produces a transient rise in blood pressure (388). 

Dopamine /3-hydroxylase is a monoxygenase that catalyzes the hydroxylation of dopamine to form norepinephrine. This enzyme is localized in the chromaffin granules of the adrenal medulla and in the storage vesicles of central and peripheral catecholaminergic neurons. Since these compounds are unstable, this activity is often assayed by following the formation of octopamine from tyramine. For example, in the assay developed by Feilchenfeld et al. (1982), the reactant tyramine was separated from the product octopamine by reversed-phase, ion-paired HPLC (/uBondapak C18 using a mobile phase of 17% (v/v)... 

Figure 9.10 HPLC of the assay mixture (A) prior to and (B) 13.65 minutes after addition of dopamine 0-hydroxyiidase to the assay stock sample. OCT, octopamine (3.2 min) TYR, tyramine (4.5 min). (From Feilchenfeld et al., 1982.)...

FIGURE 7.3 Effect of l-ethyl-3-methylimidazolium tertafluoroborate concentrations on retention factors (k ) of basic compounds. Symbols = octopamine o = synephrine = tyramine. (From Tang, F. et al. J. Chromatogr. A. 2006,1125,182-188. With permission from Elsevier Science.)... 

Tang, E. et al. Determination of octopamine, synephrine and tyramine in Citrns herbs by ionic hqnid improved green chromatography. /. Chromatogr. A. 2006, 1125, 182-188. 

Endogenous biogenic amines in the brain include catecholamines [NE (noradrenaline, NA), dopamine (DA), epinephrine (adrenaline)] 5-HT, histamine, and the so-called trace amines (P-phenylethylamine, tyramine, tryptamine, and octopamine). These amines have in common a arylalkylamine stmcture, and all have been implicated in the etiology of one or more psychiatric disorders and/or in therapeutic and/or adverse effects of drugs used to treat such disorders. In this review on depression, the focus in the case of biogenic amines will be on 5-HT, NE, and DA, although epinephrine and histamine and trace amines have also been implicated (see the section on Other Antidepressant Approaches and Targets ). 

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