Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the classical monoamines, they are present in trace concentrations. They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...

. Although they can be synthesized within parent monoamine

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...

systems, there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems. Trace amines play significant roles in regulating the quantity of monoamine neurotransmitters in the synaptic cleft of monoamine neurons with . They have well-characterized presynaptic ''amphetamine-like'' effects on these monoamine neurons via TAAR1 activation; specifically, by activating TAAR1 in neurons they promote the release and prevent reuptake of monoamine neurotransmitters from the synaptic cleft as well as inhibit

neuronal firing An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ca ...

. Phenethylamine and amphetamine possess analogous

pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...

in human dopamine neurons, as both compounds induce efflux from vesicular monoamine transporter 2 (VMAT2) and activate TAAR1 with comparable efficacy. Like

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

, and

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

, the trace amines have been implicated in a vast array of human disorders of affect and cognition, such as ADHD, depression and

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...

, among others. Trace aminergic hypo-function is particularly relevant to ADHD, since urinary and plasma phenethylamine concentrations are significantly lower in individuals with ADHD relative to controls and the two most commonly prescribed drugs for ADHD, amphetamine and

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...

, increase phenethylamine biosynthesis in treatment-responsive individuals with ADHD. A

systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...

of ADHD biomarkers also indicated that urinary phenethylamine levels could be a diagnostic biomarker for ADHD.

List of trace amines

The human trace amines include: * Phenethylamines (related to catecholamines): ** Phenethylamine (PEA) ** ''N''-Methylphenethylamine (endogenous amphetamine isomer) ** Phenylethanolamine ** ''m''-Tyramine ** ''p''-Tyramine **

3-Methoxytyramine 3-Methoxytyramine (3-MT), also known as 3-methoxy-4-hydroxyphenethylamine, is a human trace amine that occurs as a metabolite of the neurotransmitter dopamine. It is formed by the introduction of a methyl group to dopamine by the enzyme cate ...

** ''N''-Methyltyramine ** ''m''-Octopamine ** ''p''-Octopamine ** Synephrine * Tryptamine While not trace amines themselves, the classical monoamines

, and

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...

are all

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...

s at the human TAAR1 receptor;

is a high-affinity

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...

at human TAAR1. and are endogenous amines in humans, however, their human TAAR1 binding has not been determined

History

A thorough review of trace amine-associated receptors that discusses the historical evolution of this research particularly well is that of Grandy.

Notes

References

{{Neurotransmitters TAAR1 agonists Amines Amphetamine Neurotransmitters Neurochemistry

List of trace amines

History

See also

Notes

References