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94

 Functional Assessment of Urinary Neuro-biogenic Amines—A COMPREHENSIVE GUIDE

levels may affect artery resistance (va-

soconstriction) and serotonin signaling.

Inhibitory effects of serotonin may be

potentiated by tryptamine. Clinically,

trace amines are generally considered

sympathomimetic (they mimic the ac-

tion of sympathetic nerve stimulation),

they may affect vasoconstriction and

blood pressure. In large, supra-physio-

logic doses, the effects of trace amines

are similar to amphetamines.

Effects:

Decreased

tryptamine levels or defi-

cient trace amine functions may be as-

sociated with some depressive disorders.

Aromatic amino acid decarboxylase

(AADC) metabolizes tyrosine, tryp-

tophan into the trace amines tyramine

and tryptamine. Activation of mono-

amine neurotransmitter receptors (via

receptor agonists or electrical stimula-

tion) decreases AADC activity and trace

amine levels. Reserpine may deplete

CNS levels of trace amines. Multiple

studies demonstrate that loss of neurons

in specific brain areas or loss of specific

types of neurons may result in decreased

trace amine levels. Loss of D-neurons

containing AADC has been associated

with some forms of schizophrenia. The

function of both trace amine–associat-

ed receptors (TAARs) and the level of

trace amines are thought to contribute

to altered brain activity. Low levels of

tryptamine may result if the level of

the precursor amino acid tryptophan is

deficient.

Excess

tryptamine and increased

AADC activity have been associat-

ed with some forms of schizophrenia.

Increases inAADC activity may increase

trace amine levels, without affecting lev-

els of monoamine neurotransmitters.

Decreased monoamine neurotransmit-

ter receptor activation (receptor antag-

onists, neurotransmitter depletion) may

result in an increase in AADC activity

and increased trace amine levels. Urinary

tryptamine levels seem to correlate with

symptom severity in schizophrenia.

Methylated tryptamines may also play

a role in the development of schizo-

phrenia. Methylated tryptamines, such

as N,N-dimethyltryptamine (DMT),

are produced within the body, and may

have hallucinogenic effects.

Trace amines may be generated in

the gastrointestinal tract by protein-fer-

menting gut bacteria after a protein-rich

meal, and they may be found in a variety

of foods as the result of food spoilage or

deliberate fermentation. Dietary trace

amines are usually metabolized quick-

ly by MAO enzymes. Elevated levels of

trace amines may occur due to phenyl-

ketonuria, ergot poisoning or the use of

MAO inhibitors.

Synthesis and Metabolism:

Tyramine

5-HIAA

Tryptophan

Tryptamine

5-HTP

Serotonin

MAO-A/B

TPH2

(brain)

AADC

MAO-A

ALDH

AADC

TPH1

(bodypinealgland)