Trace amines

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, andserotonin, the trace amines have been implicated in a vast array of human disorders of affect and cognition, such as ADHD,[3][4]depression[3][4] and schizophrenia,[3][4] among others.[3][4] 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.[3][10]

A thorough review of trace amine-associated receptors that discusses the historical evolution of this research particularly well is that of Grandy.[11]

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