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'''Trace amines''' are an endogenous group of ]<ref name="pmid22038157">{{cite journal | author = Panas MW, Xie Z, Panas HN, Hoener MC, Vallender EJ, Miller GM | title = Trace amine associated receptor 1 signaling in activated lymphocytes | journal = J Neuroimmune Pharmacol | volume = 7 | issue = 4 | pages = 866–76 | year = 2012 | month = December | pmid = 22038157 | pmc = 3593117 | doi = 10.1007/s11481-011-9321-4 | quote = Trace Amine Associated Receptor 1 (TAAR1) is a G protein coupled receptor (GPCR) that responds to a wide spectrum of agonists, including endogenous trace amines, ...}}</ref> – and hence, monoaminergic ]<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> – that are structurally and metabolically related to classical ]s.<ref name="Vascular" /> Compared to the classical monoamines, they are present in trace concentrations.<ref name="Vascular" /> They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of ].<ref name="Vascular" /><ref name="Miller" /> Although they can be synthesized within parent monoamine ] systems,<ref name="E Weihe" /> there is evidence that suggests that some of them may comprise their own independent ]s.<ref name="Burchett">{{cite journal | author = Burchett SA, Hicks TP | title = The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain | journal = Prog. Neurobiol. | volume = 79 | issue = 5–6 | pages = 223–46 | year = 2006 | month = August | pmid = 16962229 | doi = 10.1016/j.pneurobio.2006.07.003 | url = }}</ref> |
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'''Trace amines''' are an endogenous group of ]<ref name="pmid22038157">{{cite journal | author = Panas MW, Xie Z, Panas HN, Hoener MC, Vallender EJ, Miller GM | title = Trace amine associated receptor 1 signaling in activated lymphocytes | journal = J Neuroimmune Pharmacol | volume = 7 | issue = 4 | pages = 866–76 | year = 2012 | month = December | pmid = 22038157 | pmc = 3593117 | doi = 10.1007/s11481-011-9321-4 | quote = Trace Amine Associated Receptor 1 (TAAR1) is a G protein coupled receptor (GPCR) that responds to a wide spectrum of agonists, including endogenous trace amines, ...}}</ref> – and hence, monoaminergic ]<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> – that are structurally and metabolically related to classical ]s.<ref name="Vascular" /> Compared to the classical monoamines, they are present in trace concentrations.<ref name="Vascular" /> They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of ].<ref name="Vascular" /><ref name="Miller" /> Although they can be synthesized within parent monoamine ] systems,<ref name="E Weihe" /> there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.<ref name="Burchett">{{cite journal | author = Burchett SA, Hicks TP | title = The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain | journal = Prog. Neurobiol. | volume = 79 | issue = 5–6 | pages = 223–46 | year = 2006 | month = August | pmid = 16962229 | doi = 10.1016/j.pneurobio.2006.07.003 | url = }}</ref> |
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Trace amines play very significant roles in the regulation of monoamine synapses in neurons with {{nowrap|co-localized}} {{abbr|TAAR1|trace amine-associated receptor 1}}.<ref name="Miller" /> They have well-characterized presynaptic ''amphetamine-like'' effects on monoamine neurons via ] activation;<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> specifically, they release and prevent reuptake of ] from the ].<ref name="Miller"/> Phenethylamine even happens to have has the same ] as regular amphetamine in human ]s, as both compounds induce efflux from ] (VMAT2)<ref name="E Weihe">{{cite journal | author = Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Ann. N. Y. Acad. Sci. | volume = 1216 | issue = | pages = 86–98 |date=January 2011 | pmid = 21272013 | doi = 10.1111/j.1749-6632.2010.05906.x | quote= neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC).}}</ref><ref name="Offermanns">{{cite book | editor1=Offermanns, S | editor2= Rosenthal, W| title=Encyclopedia of Molecular Pharmacology |year=2008|publisher=Springer|location=Berlin|isbn=3540389164|pages=1219–1222|edition=2nd}}</ref> and activate ] with comparable efficacy.<ref name="Miller" /> Like ], ], and ], the trace amines have been implicated in a vast array of human disorders of affect and cognition, such as ],<ref name="Neuropsychopharm">{{cite journal | author = Berry MD | title = The potential of trace amines and their receptors for treating neurological and psychiatric diseases | journal = Rev Recent Clin Trials | volume = 2 | issue = 1 | pages = 3–19 | year = 2007 | month = January | pmid = 18473983 | doi = | quote = changes in trace amines, in particular PE, have been identified as a possible factor for the onset of attention deficit/hyperactivity disorder (ADHD) . PE has been shown to induce hyperactivity and aggression, two of the cardinal clinical features of ADHD, in experimental animals . Hyperactivity is also a symptom of phenylketonuria, which as discussed above is associated with a markedly elevated PE turnover . Further, amphetamines, which have clinical utility in ADHD, are good ligands at trace amine receptors . Of possible relevance in this aspect is modafanil, which has shown beneficial effects in ADHD patients and has been reported to enhance the activity of PE at TAAR1 . Conversely, methylphenidate, which is also clinically useful in ADHD, showed poor efficacy at the TAAR1 receptor . In this respect it is worth noting that the enhancement of functioning at TAAR1 seen with modafanil was not a result of a direct interaction with TAAR1 .<br />More direct evidence has been obtained recently for a role of trace amines in ADHD. Urinary PE levels have been reported to be decreased in ADHD patients in comparison to both controls and patients with autism . Evidence for a decrease in PE levels in the brain of ADHD patients has also recently been reported . In addition, decreases in the urine and plasma levels of the PE metabolite phenylacetic acid and the precursors phenylalanine and tyrosine have been reported along with decreases in plasma tyramine . Following treatment with methylphenidate, patients who responded positively showed a normalization of urinary PE, whilst non-responders showed no change from baseline values .}}</ref><ref name="Renaissance GPCR" /> ]<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> and ],<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> among others.<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> Trace aminergic hypo-function is particularly relevant to ], since the two most commonly prescribed drugs for ADHD, ] and ], increase phenethylamine biosynthesis in treatment-responsive individuals with ADHD.<ref name="Neuropsychopharm" /> |
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Trace amines play significant roles in regulating the quantity of neurotransmitters in the ]] of monoamine neurons with {{nowrap|co-localized}} {{abbr|TAAR1|trace amine-associated receptor 1}}.<ref name="Miller" /> They have well-characterized presynaptic ''amphetamine-like'' effects on these monoamine neurons via ] activation;<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> specifically, they release and prevent reuptake of neurotransmitters from the synaptic cleft.<ref name="Miller"/> Phenethylamine even happens to have has the same ] as regular amphetamine in human ]s, as both compounds induce efflux from ] (VMAT2)<ref name="E Weihe">{{cite journal | author = Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Ann. N. Y. Acad. Sci. | volume = 1216 | issue = | pages = 86–98 |date=January 2011 | pmid = 21272013 | doi = 10.1111/j.1749-6632.2010.05906.x | quote= neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC).}}</ref><ref name="Offermanns">{{cite book | editor1=Offermanns, S | editor2= Rosenthal, W| title=Encyclopedia of Molecular Pharmacology |year=2008|publisher=Springer|location=Berlin|isbn=3540389164|pages=1219–1222|edition=2nd}}</ref> and activate ] with comparable efficacy.<ref name="Miller" /> Like ], ], and ], the trace amines have been implicated in a vast array of human disorders of affect and cognition, such as ],<ref name="Neuropsychopharm">{{cite journal | author = Berry MD | title = The potential of trace amines and their receptors for treating neurological and psychiatric diseases | journal = Rev Recent Clin Trials | volume = 2 | issue = 1 | pages = 3–19 | year = 2007 | month = January | pmid = 18473983 | doi = | quote = changes in trace amines, in particular PE, have been identified as a possible factor for the onset of attention deficit/hyperactivity disorder (ADHD) . PE has been shown to induce hyperactivity and aggression, two of the cardinal clinical features of ADHD, in experimental animals . Hyperactivity is also a symptom of phenylketonuria, which as discussed above is associated with a markedly elevated PE turnover . Further, amphetamines, which have clinical utility in ADHD, are good ligands at trace amine receptors . Of possible relevance in this aspect is modafanil, which has shown beneficial effects in ADHD patients and has been reported to enhance the activity of PE at TAAR1 . Conversely, methylphenidate, which is also clinically useful in ADHD, showed poor efficacy at the TAAR1 receptor . In this respect it is worth noting that the enhancement of functioning at TAAR1 seen with modafanil was not a result of a direct interaction with TAAR1 .<br />More direct evidence has been obtained recently for a role of trace amines in ADHD. Urinary PE levels have been reported to be decreased in ADHD patients in comparison to both controls and patients with autism . Evidence for a decrease in PE levels in the brain of ADHD patients has also recently been reported . In addition, decreases in the urine and plasma levels of the PE metabolite phenylacetic acid and the precursors phenylalanine and tyrosine have been reported along with decreases in plasma tyramine . Following treatment with methylphenidate, patients who responded positively showed a normalization of urinary PE, whilst non-responders showed no change from baseline values .}}</ref><ref name="Renaissance GPCR" /> ]<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> and ],<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> among others.<ref name="Neuropsychopharm" /><ref name="Renaissance GPCR" /> Trace aminergic hypo-function is particularly relevant to ], since the two most commonly prescribed drugs for ADHD, ] and ], increase phenethylamine biosynthesis in treatment-responsive individuals with ADHD.<ref name="Neuropsychopharm" /> |
L-Phenylalanine
L-Tyrosine
L-DOPA
Epinephrine
Phenethylamine
p-Tyramine
Dopamine
Norepinephrine
N-Methylphenethylamine
N-Methyltyramine
p-Octopamine
Synephrine
3-Methoxytyramine
AADC
AADC
AADC
primary
Phenethylaminergic trace amines and the catecholamines are derivatives of phenylalanine.
