Norepinephrine is a monoamine neurotransmitter
Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain (-CH2-CH2-). All monoamines are derived from aromatic amino acids like phenylalanine, tyrosine, tryptophan, and the thyroid hormones by the action of aromatic amino acid decarboxylase enzymes. Monoaminergic systems, i.e., the networks of neurons that utilize monoamine neurotransmitters, are involved in the regulation of cognitive processes such as emotion, arousal, and certain types of memory. It has been found that monoamine neurotransmitters play an important role in the secretion and production of neurotrophin-3 by astrocytes, a chemical which maintains neuron integrity and provides neurons with trophic support.[1] Drugs used to increase (or reduce) the effect of monoamine are sometimes used to treat patients with psychiatric disorders, including depression, anxiety, and schizophrenia.[2]
Contents
- 1 Examples
- 2 Evolution
- 3 Disorders
- 4 See also
- 5 References
- 6 External links
Examples
Part of this section is transcluded from Trace amine. (edit | history)
Human biosynthesis pathway for trace amines and catecholamines[3][4]
L-Phenylalanine
L-Tyrosine
L-Dopa
Epinephrine
Phenethylamine
p-Tyramine
Dopamine
Norepinephrine
N-Methylphenethylamine
N-Methyltyramine
p-Octopamine
Synephrine
3-Methoxytyramine
AADC
AADC
AADC
PNMT
PNMT
PNMT
PNMT
AAAH
AAAH
COMT
DBH
DBH
Phenethylaminergic trace amines and the catecholamines are derivatives of phenylalanine.
- Classical monoamines
- Histamine[5]
- Catecholamines:
- Adrenaline (Ad; Epinephrine, Epi)
- Dopamine (DA)
- Noradrenaline (NAd; Norepinephrine, NE)
- Classical Tryptamines:
- Serotonin (5-HT)
- Melatonin
- Trace amines
- Phenethylamines (related to catecholamines):
- Phenethylamine[6][7] (PEA)
- N-Methylphenethylamine[8][6] (endogenous amphetamine isomer)
- Phenylethanolamine[9]
- m-Tyramine[6]
- p-Tyramine[6]
- N-Methyltyramine[8][6]
- m-Octopamine[6]
- p-Octopamine[6]
- Synephrine[8]
- 3-Methoxytyramine[8]
- Thyronamine compounds:
- Tryptamine[8][7]
Specific transporter proteins called monoamine transporters that transport monoamines in or out of a cell exist. These are the dopamine transporter (DAT), serotonin transporter (SERT), and the norepinephrine transporter (NET) in the outer cell membrane and the vesicular monoamine transporter (VMAT1 and VMAT2) in the membrane of intracellular vesicles.[citation needed]
After release into the synaptic cleft, monoamine neurotransmitter action is ended by reuptake into the presynaptic terminal. There, they can be repackaged into synaptic vesicles or degraded by the enzyme monoamine oxidase (MAO), which is a target of monoamine oxidase inhibitors, a class of antidepressants.[citation needed]
Evolution
A phylogenetic tree showing how a number of monoamine receptors are related to each other.
As demonstrated by the wide existence of monoamine transmitters, an organism's ability to modify its behavior is advantageous to its survival. This system is found in various species such as nematodes, lobsters, desert locusts, hens, mice and zebra finches.[10]
Disorders
Disorders of monoamine neurotransmitters exist, part of a growing number of neurotransmitter disorders identified. Such disorders are responsible for biosynthesis degradation and difficulty in transporting neurotransmitters such as dopamine, norepinephrine, epinephrine, or serotonin. Monoamine neurotransmitter disorders mimic the symptoms of other more prevalent neurological disorders (e.g. cerebral palsy) and thus are frequently misdiagnosed.[2]
See also
- 5-HT2c receptor agonist
- Monoamine oxidase
- Monoamine transporter
- Neurotransmitter
- Monoamine Hypothesis
- Biogenic amine
- Trace amine
References
- ^ Mele, Tina; Čarman-Kržan, Marija; Jurič, Damijana Mojca (2010). "Regulatory role of monoamine neurotransmitters in astrocytic NT-3 synthesis". International Journal of Developmental Neuroscience 28 (1): 13–9. doi:10.1016/j.ijdevneu.2009.10.003. PMID 19854260.
- ^ a b Kurian, Manju A; Gissen, Paul; Smith, Martin; Heales, Simon JR; Clayton, Peter T (2011). "The monoamine neurotransmitter disorders: An expanding range of neurological syndromes". The Lancet Neurology 10 (8): 721–33. doi:10.1016/S1474-4422(11)70141-7. PMID 21777827.
- ^ Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186.
- ^ Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.
- ^ Romero-Calderón R, Uhlenbrock G, Borycz J, Simon AF, Grygoruk A, Yee SK, Shyer A, Ackerson LC, Maidment NT, Meinertzhagen IA, Hovemann BT, Krantz DE (November 2008). "A glial variant of the vesicular monoamine transporter is required to store histamine in the Drosophila visual system". PLoS Genet. 4 (11): e1000245. doi:10.1371/journal.pgen.1000245. PMC 2570955. PMID 18989452.
- ^ a b c d e f g Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186.
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 ...
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 ...
- ^ a b c Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.
- ^ a b c d e Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.
In addition to the main metabolic pathway, TAs can also be converted by nonspecific N-methyltransferase (NMT) [22] and phenylethanolamine N-methyltransferase (PNMT) [23] to the corresponding secondary amines (e.g. synephrine [14], N-methylphenylethylamine and N-methyltyramine [15]), which display similar activities on TAAR1 (TA1) as their primary amine precursors...Both dopamine and 3-methoxytyramine, which do not undergo further N-methylation, are partial agonists of TAAR1 (TA1). ...
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 [7,8,36]. Clinical studies report increased β-PEA plasma levels in patients suffering from acute schizophrenia [37] and elevated urinary excretion of β-PEA in paranoid schizophrenics [38], 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’ [39]
- ^ Wainscott DB, Little SP, Yin T, Tu Y, Rocco VP, He JX, Nelson DL (January 2007). "Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1". The Journal of Pharmacology and Experimental Therapeutics 320 (1): 475–85. doi:10.1124/jpet.106.112532. PMID 17038507.
- ^ Lövheim, Hugo (2012). "A new three-dimensional model for emotions and monoamine neurotransmitters". Medical Hypotheses 78 (2): 341–8. doi:10.1016/j.mehy.2011.11.016. PMID 22153577.
External links
- Biogenic monoamines at the US National Library of Medicine Medical Subject Headings (MeSH)
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Neurotransmitters
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| Amino acid-derived |
- Major excitatory/inhibitory systems: Glutamate system: Agmatine
- Aspartic acid (aspartate)
- Cycloserine
- Glutamic acid (glutamate)
- Glutathione
- Glycine
- GSNO
- GSSG
- Kynurenic acid
- NAA
- NAAG
- Proline
- Serine; GABA system: GABA
- GABOB
- GHB; Glycine system: α-Alanine
- β-Alanine
- Glycine
- Hypotaurine
- Proline
- Sarcosine
- Serine
- Taurine; GHB system: GHB
- T-HCA (GHC)
- Biogenic amines: Monoamines: 6-OHM
- Dopamine
- Epinephrine (adrenaline)
- Melatonin
- NAS (normelatonin)
- Norepinephrine (noradrenaline)
- Serotonin (5-HT); Trace amines:
- 3-Iodothyronamine
- N-Methylphenethylamine
- N-Methyltryptamine
- m-Octopamine
- p-Octopamine
- Phenylethanolamine
- Phenethylamine
- Synephrine
- Tryptamine
- m-Tyramine
- p-Tyramine; Others: Histamine
- Neuropeptides: See here instead.
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| Lipid-derived |
- Endocannabinoids: 2-AG
- 2-AGE (noladin ether)
- 2-ALPI
- 2-OG
- AA-5-HT
- Anandamide (AEA)
- DEA
- LPI
- NADA
- NAGly
- OEA
- Oleamide
- PEA
- RVD-Hpα
- SEA
- Virodhamine (O-AEA)
- Neurosteroids: See here instead.
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| Nucleobase-derived |
- Nucleosides: Adenosine system: Adenosine
- ADP
- AMP
- ATP
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| Vitamin-derived |
- Cholinergic system: Acetylcholine
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| Miscellaneous |
- Gasotransmitters: Carbon monoxide (CO)
- Hydrogen sulfide (H2S)
- Nitrous oxide (NO); Candidates: Acetaldehyde
- Ammonia (NH3)
- Carbonyl sulfide (COS)
- Nitrous oxide (N2O)
- Sulfur dioxide (SO2)
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TAAR ligands in humans
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| TAAR1 |
| Agonists |
| Endogenous† |
- Classical monoamine neurotransmitters
- Dopamine
- Histamine
- Norepinephrine
- Serotonin
- Trace amines
- 3-Iodothyronamine
- 3-Methoxytyramine
- N-Methylphenethylamine
- N-Methyltyramine
- m-Octopamine
- p-Octopamine
- Phenethylamine
- Phenylethanolamine
- Synephrine
- Tryptamine
- m-Tyramine
- p-Tyramine
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| Synthetic‡ |
- Amphetamine
- DOB
- DOET
- 4-Hydroxyamphetamine
- Isoprenaline
- MDA
- MDMA
- 2-Methylphenethylamine
- 3-Methylphenethylamine
- 4-Methylphenethylamine
- β-Methylphenethylamine
- Methamphetamine
- 3-MMA
- Norfenfluramine
- Phentermine
- o-PIT
- Propylhexedrine
- RO5166017
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| Antagonists |
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| TAAR2 |
| Agonists‡ |
- 3-Iodothyronamine
- Phenethylamine
- Tyramine
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| Antagonists |
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| TAAR5 |
| Agonists‡ |
- Dimethylethylamine
- Trimethylamine
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| Antagonists‡ |
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†References for all endogenous human TAAR1 ligands are provided at List of trace amines
‡References for synthetic TAAR1 agonists can be found at TAAR1 or in the associated compound articles. For TAAR2 and TAAR5 agonists and antagonists, see TAAR for references.
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