Trace amine
| Trace amine | |
|---|---|
| Drug class | |
Phenethylamine skeleton
|
|
| Class identifiers | |
| Mechanism of action | Receptor agonist |
| Biological target | Trace amine-associated receptor 1 |
| Chemical class | Endogenous amines with trace occurrence |
| External links | |
| MeSH | C434723 |
Trace amines are an endogenous group of trace amine associated receptor 1 (TAAR1) agonists[1] – and hence, monoaminergic neuromodulators[2][3][4] – that are structurally and metabolically related to classical monoamine neurotransmitters.[5] Compared to the classical monoamines, they are present in trace concentrations.[5] They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism.[5][6] Although they can be synthesized within parent monoamine neurotransmitter systems,[7] there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.[2]
Trace amines play significant roles in regulating the quantity of monoamine neurotransmitters in the synaptic cleft of monoamine neurons with co-localized TAAR1.[6] They have well-characterized presynaptic amphetamine-like effects on these monoamine neurons via TAAR1 activation;[3][4] specifically, by activating TAAR1 in neurons they promote the release[note 1] and prevent reuptake of monoamine neurotransmitters from the synaptic cleft as well as inhibit postsynaptic neuronal firing.[6][8] Phenethylamine and amphetamine possess analogous pharmacodynamics in human dopamine neurons, as both compounds induce efflux from vesicular monoamine transporter 2 (VMAT2)[7][9] and activate TAAR1 with comparable efficacy.[6] 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,[3][4][10] depression[3][4] and schizophrenia,[2][3][4] among others.[3][4][10]
A thorough review of trace amine-associated receptors that discusses the historical evolution of this research particularly well is that of Grandy.[11]
List of trace amines
The human trace amines include:
- Phenethylamines (related to catecholamines):
- Thyronamine compounds:
- Tryptamine[4][6]
While not trace amines themselves, the classical monoamines dopamine, norepinephrine, serotonin, and histamine are all partial TAAR1 agonists in humans.[6] N-Methyltryptamine and N,N-dimethyltryptamine are endogenous amines in humans, however their human TAAR1 binding has not yet been documented.[2]
See also
Notes
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