| Revision as of 09:38, 27 May 2014 editSeppi333 (talk | contribs)Autopatrolled, Extended confirmed users, Page movers, New page reviewers, Pending changes reviewers, Template editors35,345 edits guess this isnt surprising. might have to update my diagram >.>← Previous edit |
Revision as of 00:08, 28 May 2014 edit undoSeppi333 (talk | contribs)Autopatrolled, Extended confirmed users, Page movers, New page reviewers, Pending changes reviewers, Template editors35,345 editsm moving a ref and turning part of this page into a transclusion templateNext edit → |
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'''Trace amines''' are an endogenous group of ]s<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">{{cite journal | author = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = J. Neurochem. | volume = 116 | issue = 2 | pages = 164–176 |date=January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref> 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 ]s<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 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 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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The human trace amines include: |
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The human trace amines include: |
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{{Phenylalanine biosynthesis|header=Metabolic pathway of phenylalanine|caption=Phenethylaminergic trace amines and the catecholamines are derivatives of phenylalanine.|align=right}} |
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{{Phenylalanine biosynthesis|header=Metabolic pathway of phenylalanine|caption=Phenethylaminergic trace amines and the catecholamines are derivatives of phenylalanine.|align=right}}<onlyinclude>{{#ifeq:{{{transcludesection|TA list}}}|TA list| |
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*]s (related to ]s): |
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** ]<ref name="Vascular">{{cite journal | author = Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacol. Ther. | volume = 125 | issue = 3 | pages = 363–375 |date=March 2010 | pmid = 19948186 | doi = 10.1016/j.pharmthera.2009.11.005 | quote= Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 1.4.3.4) (Berry, 2004) (Fig. 2) ... It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone ... Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut ...<br /> Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life ...}}</ref><ref name="Miller" /> (PEA) |
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** ]<ref name="Vascular">{{cite journal | author = Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacol. Ther. | volume = 125 | issue = 3 | pages = 363–375 |date=March 2010 | pmid = 19948186 | doi = 10.1016/j.pharmthera.2009.11.005 | quote= Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 1.4.3.4) (Berry, 2004) (Fig. 2) ... It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone ... Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut ...<br /> Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life ...}}</ref><ref name="Miller" /> (PEA) |
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The dysregulation of TA levels has been linked to several diseases, which highlights the corresponding members of the TAAR family as potential targets for drug development. In this article, we focus on the relevance of TAs and their receptors to nervous system-related disorders, namely schizophrenia and depression; however, TAs have also been linked to other diseases such as migraine, attention deficit hyperactivity disorder, substance abuse and eating disorders . Clinical studies report increased β-PEA plasma levels in patients suffering from acute schizophrenia and elevated urinary excretion of β-PEA in paranoid schizophrenics , which supports a role of TAs in schizophrenia. As a result of these studies, β-PEA has been referred to as the body’s ‘endogenous amphetamine’ }}</ref> |
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The dysregulation of TA levels has been linked to several diseases, which highlights the corresponding members of the TAAR family as potential targets for drug development. In this article, we focus on the relevance of TAs and their receptors to nervous system-related disorders, namely schizophrenia and depression; however, TAs have also been linked to other diseases such as migraine, attention deficit hyperactivity disorder, substance abuse and eating disorders . Clinical studies report increased β-PEA plasma levels in patients suffering from acute schizophrenia and elevated urinary excretion of β-PEA in paranoid schizophrenics , which supports a role of TAs in schizophrenia. As a result of these studies, β-PEA has been referred to as the body’s ‘endogenous amphetamine’ }}</ref> |
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*] compounds: |
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**]<ref name="Miller">{{cite journal | author = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = J. Neurochem. | volume = 116 | issue = 2 | pages = 164–176 |date=January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref> |
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**]<ref name="Miller" /> |
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*]s (], related to ]): |
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*]s (], related to ]): |
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** ]<ref name="Miller" /> |
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** ]<ref name="Miller" /> |
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** ]<ref name="Renaissance GPCR" /> |
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** ]<ref name="Renaissance GPCR" /> |
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}}</onlyinclude> |
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While not trace amines themselves, the classical monoamines ], ], ], and ] are all partial TAAR1 agonists in humans.<ref name="Miller" /> |
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While not trace amines themselves, the classical monoamines ], ], ], and ] are all partial TAAR1 agonists in humans.<ref name="Miller" /> |
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Trace amines play very significant roles in the regulation of monoamine synapses in neurons with co-localized TAAR1. They have well-characterized presynaptic amphetamine-like effects on monoamine neurons via TAAR1 activation; specifically, they release and prevent reuptake of neurotransmitters from the synaptic cleft. Phenethylamine even happens to have has 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.
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.
