Trace amines are an endogenous group of trace amine associated receptor 1 (TAAR1) agonists â€" and hence, monoaminergic neuromodulators â€" 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. Although they can be synthesized within parent monoamine neurotransmitter 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 neurotransmitters in the synaptic cleft of monoamine neurons with co-localized TAAR1. They have well-characterized presynaptic amphetamine-like effects on these monoamine neurons via TAAR1 activation; specifically, they release and prevent reuptake of neurotransmitters from the synaptic cleft. Phenethylamine even happens to have the same pharmacodynamics as regular amphetamine in human dopamine neurons, as both compounds induce efflux from vesicular monoamine transporter 2 (VMAT2) and activate TAAR1 with comparable efficacy. Like dopamine, noradrenaline, and serotonin, the trace amines have been implicated in a vast array of human disorders of affect and cognition, such as ADHD, depression and schizophrenia, among others. Trace aminergic hypo-function is particularly relevant to ADHD, since the two most commonly prescribed drugs for ADHD, amphetamine and methylphenidate, increase phenethylamine biosynthesis in treatment-responsive individuals with ADHD.
A thorough review of trace amine-associated receptors that discusses the historical evolution of this research particularly well is that of Grandy.
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
- N-Methyltyramine
- m-Octopamine
- p-Octopamine
- Synephrine
- 3-Methoxytyramine
- Thyronamine compounds:
- 3-Iodothyronamine
- Tryptamines (indoleamines, related to serotonin):
- Tryptamine
- N-Methyltryptamine
While not trace amines themselves, the classical monoamines dopamine, norepinephrine, serotonin, and histamine are all partial TAAR1 agonists in humans. N,N-Dimethyltryptamine is an endogenous amine in humans and a known rat TAAR1 agonist, but its human TAAR1 binding has not yet been documented; some ligands at rat TAAR1 have no affinity at human TAAR1 (e.g., LSD).
See also
- Monoamine neurotransmitters
- Trace amine-associated receptor 1