PHENETHYLAMINE (PEA), also known as β-PHENYLETHYLAMINE (β-PEA) and
2-PHENYLETHAN-1-AMINE, is an organic compound , natural monoamine
alkaloid , and trace amine which acts as a central nervous system
stimulant in humans.
Phenylethylamine functions as a monoaminergic neuromodulator and, to
a lesser extent, a neurotransmitter in the human central nervous
system . It is biosynthesized from the amino acid
enzymatic decarboxylation via the enzyme aromatic L-amino acid
decarboxylase . In addition to its presence in mammals,
phenethylamine is found in many other organisms and foods, such as
chocolate , especially after microbial fermentation . It is sold as a
dietary supplement for purported mood and weight loss -related
therapeutic benefits ; however, orally ingested phenethylamine is
primarily metabolized in the small intestine by monoamine oxidase B
(MAO-B) and then aldehyde dehydrogenase (ALDH), which convert it to
phenylacetic acid . This prevents significant concentrations from
reaching the brain when taken in low doses.
Phenethylamines, or more properly, substituted phenethylamines are
the group of phenethylamine derivatives which contain phenethylamine
as a "backbone"; in other words, this chemical class includes
derivative compounds that are formed by replacing one or more hydrogen
atoms in the phenethylamine core structure with substituents . The
class of substituted phenethylamines includes all substituted
amphetamines , and substituted methylenedioxyphenethylamines (MDxx),
and contains many drugs which act as empathogens , stimulants ,
psychedelics , anxiolytics (hypnotics ) and entactogens , anorectics ,
bronchodilators , decongestants , and/or antidepressants , among
* 1 Natural occurrence
* 2 Chemistry
* 2.1 Substituted derivatives
* 2.2 Synthesis
* 2.3 Detection in body fluids
* 3 Pharmacology
* 3.1 Pharmacodynamics
* 4 See also
* 5 Notes
* 6 References
* 7 External links
Phenethylamine is produced by a wide range of species throughout the
plant and animal kingdoms, including humans; it is also produced by
certain fungi and bacteria (genus:
Pseudomonas , and
Enterobacteriaceae ) and acts as a potent
anti-microbial against certain pathogenic strains of Escherichia coli
(e.g., the O157:H7 strain ) at sufficient concentrations.
Phenethylamine is a primary amine, the amino-group being attached to
a benzene ring through a two-carbon, or ethyl group . It is a
colourless liquid at room temperature that has a fishy odour, and is
soluble in water, ethanol and ether . Its density is 0.964 g/ml and
its boiling point is 195 °C. Upon exposure to air, it combines with
carbon dioxide to form a solid carbonate salt .
strongly basic , pKb = 4.17 (or pKa = 9.83), as measured using the HCl
salt and forms a stable crystalline hydrochloride salt with a melting
point of 217 °C.
Substituted phenethylamines are a chemical class of organic compounds
that are based upon the phenethylamine structure; the class is
composed of all the derivative compounds of phenethylamine which can
be formed by replacing, or substituting , one or more hydrogen atoms
in the phenethylamine core structure with substituents .
Many substituted phenethylamines are psychoactive drugs which belong
to a variety of different drug classes, including central nervous
system stimulants (e.g., amphetamine ), hallucinogens (e.g.,
2,5-dimethoxy-4-methylamphetamine ), entactogens (e.g.,
3,4-methylenedioxyamphetamine ), appetite suppressants (e.g.
phentermine ), nasal decongestants and bronchodilators (e.g.,
pseudoephedrine ), antidepressants (e.g. bupropion ), antiparkinson
agents (e.g., selegiline ), and vasopressors (e.g., ephedrine ), among
others. Many of these psychoactive compounds exert their
pharmacological effects primarily by modulating monoamine
neurotransmitter systems; however, there is no mechanism of action or
biological target that is common to all members of this subclass.
Numerous endogenous compounds – including hormones , monoamine
neurotransmitters, and many trace amines (e.g., dopamine ,
norepinephrine , adrenaline , tyramine , and others) – are
substituted phenethylamines. Several notable recreational drugs, such
MDMA (ecstasy), methamphetamine , and cathinones , are also members
of the class. All of the substituted amphetamines are phenethylamines
Pharmaceutical drugs that are substituted phenethylamines include
phenelzine , phenformin , and fanetizole , among many others.
One method for preparing β-phenethylamine, set forth in J. C.
Robinson's and H. R. Snyder's Organic Syntheses (published 1955),
involves the reduction of benzyl cyanide with hydrogen in liquid
ammonia , in the presence of a
Raney-Nickel catalyst , at a
temperature of 130 °C and a pressure of 13.8 MPa. Alternative
syntheses are outlined in the footnotes to this preparation.
A much more convenient method for the synthesis of β-phenethylamine
is the reduction of ω-nitrostyrene by lithium aluminum hydride in
ether, whose successful execution was first reported by R. F. Nystrom
and W. G. Brown in 1948.
Phenethylamine can also be produced via the cathodic reduction of
benzyl cyanide in a divided cell.
phenethylamine from benzyl cyanide
It is possible to assemble phenethylamine structures for synthesis of
compounds such as epinephrine , amphetamines , tyrosine and dopamine
by adding the beta-aminoethyl side chain to the phenyl ring. This can
be done via
Friedel-Crafts acylation with N-protected acyl chlorides
when the arene is activated, or by
Heck reaction of the phenyl with
N-vinyloxazolone , followed by hydrogenation , or by cross-coupling
with beta-amino organozinc reagents, or reacting a brominated arene
with beta-aminoethyl organolithium reagents, or by Suzuki
DETECTION IN BODY FLUIDS
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. (September 2016)
Reviews that cover attention deficit hyperactivity disorder (ADHD)
and phenethylamine indicate that several studies have found abnormally
low urinary phenethylamine concentrations in ADHD individuals when
compared with controls. In treatment responsive individuals,
amphetamine and methylphenidate greatly increase urinary
phenethylamine concentration. An ADHD biomarker review also
indicated that urinary phenethylamine levels could be a diagnostic
biomarker for ADHD.
Skydiving induces a marked increase in urinary phenethylamine
Thirty minutes of moderate to high intensity physical exercise has
been shown to induce an enormous increase in urinary phenylacetic acid
, the primary metabolite of phenethylamine. Two reviews noted a
study where the mean 24 hour urinary phenylacetic acid concentration
following just 30 minutes of intense exercise rose 77% above its base
level; the reviews suggest that phenethylamine synthesis sharply
increases during physical exercise during which it is rapidly
metabolized due to its short half-life of roughly 30 seconds. In a
resting state, phenethylamine is synthesized in catecholamine neurons
L-phenylalanine by aromatic amino acid decarboxylase at
approximately the same rate as dopamine is produced. Because of the
pharmacological relationship between phenethylamine and amphetamine,
the original paper and both reviews suggest that phenethylamine plays
a prominent role in mediating the mood-enhancing euphoric effects of a
runner\'s high , as both phenethylamine and amphetamine are potent
See also: Neurobiological effects of physical exercise §
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. (September 2016)
Phenethylamine pharmacodynamics in a TAAR1–dopamine neuron
v · t · e via AADC Both amphetamine and phenethylamine
induce neurotransmitter release from
VMAT2 and bind to
When either binds to TAAR1, it reduces neuron firing rate and triggers
protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting
in DAT phosphorylation. Phosphorylated DAT then either operates in
reverse or withdraws into the axon terminal and ceases transport.
Phenethylamine, being similar to amphetamine in its action at their
common biomolecular targets , releases norepinephrine and dopamine .
Phenethylamine also appears to induce acetylcholine release via a
Phenethylamine has been shown to bind to two human trace
amine-associated receptors , h
TAAR1 and h
TAAR2 , as an agonist.
Biosynthetic pathways for catecholamines and trace amines in the
3-Methoxytyramine AADC AADC AADC primary
pathway PNMT PNMT PNMT PNMT AAAH AAAH brain
pathway COMT DBH DBH In humans, catecholamines and
phenethylaminergic trace amines are derived from the amino acid
By oral route , phenylethylamine's half-life is 5–10 minutes;
endogenously produced PEA in catecholamine neurons has a half-life of
roughly 30 seconds. In humans, PEA is metabolized by
phenylethanolamine N-methyltransferase (PNMT), monoamine oxidase A
(MAO-A), monoamine oxidase B (MAO-B), semicarbazide-sensitive amine
oxidases (SSAOs), flavin-containing monooxygenase 3 (FMO3), and
aralkylamine N-acetyltransferase (AANAT).
N-Methylphenethylamine , an
isomer of amphetamine , is produced in humans via the metabolism of
phenethylamine by PNMT. β-
Phenylacetic acid is the primary urinary
metabolite of phenethylamine and is produced via monoamine oxidase
metabolism and subsequent aldehyde dehydrogenase metabolism.
Phenylacetaldehyde is the intermediate product which is produced by
monoamine oxidase and then further metabolized into β-phenylacetic
acid by aldehyde dehydrogenase.
When the initial phenylethylamine concentration in the brain is low,
brain levels can be increased 1000-fold when taking a monoamine
oxidase inhibitor (MAOI), particularly a
MAO-B inhibitor , and by
3–4 times when the initial concentration is high.
* ^ In other words, all of the compounds that belong to this class
are structural analogs of phenethylamine.
* ^ A B Pei Y, Asif-Malik A, Canales JJ (April 2016). "Trace Amines
and the Trace Amine-Associated Receptor 1: Pharmacology,
Neurochemistry, and Clinical Implications" . Front. Neurosci. 10: 148.
PMC 4820462 . PMID 27092049 . doi :10.3389/fnins.2016.00148 .
Furthermore, evidence has accrued on the ability of TAs to modulate
brain reward (i.e., the subjective experience of pleasure) and
reinforcement (i.e., the strengthening of a conditioned response by a
given stimulus; Greenshaw, 1984), suggesting the involvement of the
TAs in the neurological adaptations underlying drug addiction, a
chronic relapsing syndrome characterized by compulsive drug taking,
inability to control drug intake and dysphoria when access to the drug
is prevented (Koob, 2009). Consistent with its hypothesized role as
“endogenous amphetamine,” β-PEA was shown to possess reinforcing
properties, a defining feature that underlies the abuse liability of
amphetamine and other psychomotor stimulants. β-PEA was also as
effective as amphetamine in its ability to produce conditioned place
preference (i.e., the process by which an organism learns an
association between drug effects and a particular place or context) in
rats (Gilbert and Cooper, 1983) and was readily self-administered by
dogs that had a stable history (i.e., consisting of early acquisition
and later maintenance) of amphetamine or cocaine self-administration
(Risner and Jones, 1977; Shannon and Thompson, 1984). In another
study, high concentrations of β-PEA dose-dependently maintained
responding in monkeys that were previously trained to self-administer
cocaine, and pretreatment with a
MAO-B inhibitor, which delayed β-PEA
deactivation, further increased response rates (Bergman et al., 2001).
* ^ A B "Pharmacology and Biochemistry". Phenethylamine. PubChem
Compound. United States National Library of Medicine – National
Center for Biotechnology Information. Retrieved 28 December 2016.
* ^ A B C D E F G H Lindemann L, Hoener MC (2005). "A renaissance
in trace amines inspired by a novel GPCR family". Trends Pharmacol.
Sci. 26 (5): 274–281. PMID 15860375 . doi
:10.1016/j.tips.2005.03.007 . The pharmacology of TAs might also
contribute to a molecular understanding of the well-recognized
antidepressant effect of physical exercise . In addition to the
various beneficial effects for brain function mainly attributed to an
upregulation of peptide growth factors , exercise induces a rapidly
enhanced excretion of the main β-PEA metabolite β-phenylacetic acid
(b-PAA) by on average 77%, compared with resting control subjects ,
which mirrors increased β-PEA synthesis in view of its limited
endogenous pool half-life of ~30 s .
* ^ A B C "Chemical and Physical Properties". Phenethylamine.
PubChem Compound. United States National Library of Medicine –
National Center for Biotechnology Information. Retrieved 17 February
* ^ Sabelli, HC; Mosnaim, AD; Vazquez, AJ; Giardina, WJ; Borison,
RL; Pedemonte, WA (1976). "Biochemical plasticity of synaptic
transmission: A critical review of Dale's Principle". Biological
Psychiatry. 11 (4): 481–524. PMID 9160 .
* ^ A B Berry, MD (July 2004). "Mammalian central nervous system
trace amines. Pharmacologic amphetamines, physiologic
neuromodulators." (PDF). Journal of Neurochemistry. 90 (2): 257–71.
PMID 15228583 . doi :10.1111/j.1471-4159.2004.02501.x .
* ^ A B C D "Phenylethylamine". HMDB Version 3.6. Human Metabolome
Database. 11 February 2016. Retrieved 20 September 2016.
* ^ A B Yang, HY; Neff, NH (1973). "Beta-phenylethylamine: A
specific substrate for type B monoamine oxidase of brain". The Journal
of Pharmacology and Experimental Therapeutics. 187 (2): 365–71. PMID
* ^ A B Suzuki O, Katsumata Y, Oya M (1981). "Oxidation of
beta-phenylethylamine by both types of monoamine oxidase: examination
of enzymes in brain and liver mitochondria of eight species". J.
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* ^ Smith, Terence A. (1977). "
Phenethylamine and related compounds
in plants". Phytochemistry. 16 (1): 9–18. doi
* ^ A B C D E Irsfeld M, Spadafore M, Prüß BM; Spadafore; Prüß
(September 2013). "β-phenylethylamine, a small molecule with a large
impact" . Webmedcentral. 4 (9). PMC 3904499 . PMID 24482732 . While
diagnosis of ADHD is usually done by analysis of the symptoms
(American Psychiatric Association, 2000), PEA was recently described
as a biomarker for ADHD (Scassellati et al., 2012). This novel
discovery will improve the confidence of the diagnostic efforts,
possibly leading to reduced misdiagnosis and overmedication.
Specifically, the urinary output of PEA was lower in a population of
children suffering from ADHD, as compared to the healthy control
population, an observation that was paralleled by reduced PEA levels
in ADHD individuals (Baker et al., 1991; Kusaga, 2002). In a
consecutive study (Kusaga et al., 2002), those of the children
suffering with ADHD were treated with methylphenidate, also known as
Ritalin. Patients whose symptoms improved in response to treatment
with methylphenidate had a significantly higher PEA level than
patients who did not experience such an improvement in their condition
(Kusaga et al., 2002). CS1 maint: Multiple names: authors list (link )
* ^ Lynnes T, Horne SM, Prüß BM (2014). "ß-Phenylethylamine as a
novel nutrient treatment to reduce bacterial contamination due to
Escherichia coli O157:H7 on beef meat". Meat Sci. 96 (1): 165–71.
PMID 23896151 . doi :10.1016/j.meatsci.2013.06.030 . Acetoacetic acid
(AAA) and ß-phenylethylamine (PEA) performed best in this experiment.
On beef meat pieces, PEA reduced the bacterial cell count by 90% after
incubation of the PEA treated and E. coli contaminated meat pieces at
10°C for one week.
* ^ A B C D E "Phenethylamine". PubChem Compound. United States
National Library of Medicine – National Center for Biotechnology
Information. Retrieved 28 December 2016.
* ^ O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station,
NJ: Merck and Co., Inc., 2001., p. 1296
* ^ Leffler, Esther B.; Spencer, Hugh M.; Burger, Alfred (1951).
"Dissociation Constants of Adrenergic Amines". Journal of the American
Chemical Society. 73 (6): 2611–3. doi :10.1021/ja01150a055 .
* ^ Robinson, J. C.; Snyder, H. R. (1955). "β-Phenylethylamine"
(PDF). Organic Syntheses, Coll. 3: 720.
* ^ Nystrom, Robert F.; Brown, Weldon G. (1948). "Reduction of
Organic Compounds by Lithium Aluminum Hydride. III. Halides, Quinones,
Miscellaneous Nitrogen Compounds1". Journal of the American Chemical
Society. 70 (11): 3738–40. PMID 18102934 . doi :10.1021/ja01191a057
* ^ A B Krishnan, V.; Muthukumaran, A.; Udupa, H. V. K. (1979).
"The electroreduction of benzyl cyanide on iron and cobalt cathodes".
Journal of Applied Electrochemistry. 9 (5): 657–659. doi
* ^ Gary A. Molander; Fabricio Vargas (2007-01-18).
"β-Aminoethyltrifluoroborates: Efficient Aminoethylations via
Suzuki-Miyaura Cross-Coupling" . Org Lett. 9 (2): 203–206. PMC
2593899 . doi :10.1021/ol062610v .
* ^ A B C Scassellati C, Bonvicini C, Faraone SV, Gennarelli M
(October 2012). "Biomarkers and attention-deficit/hyperactivity
disorder: a systematic review and meta-analyses". J. Am. Acad. Child
Adolesc. Psychiatry. 51 (10): 1003–1019.e20. PMID 23021477 . doi
:10.1016/j.jaac.2012.08.015 . Although we did not find a sufficient
number of studies suitable for a meta-analysis of PEA and ADHD, three
studies20,57,58 confirmed that urinary levels of PEA were
significantly lower in patients with ADHD compared with controls. ...
Administration of D-amphetamine and methylphenidate resulted in a
markedly increased urinary excretion of PEA,20,60 suggesting that ADHD
treatments normalize PEA levels. ... Similarly, urinary biogenic trace
amine PEA levels could be a biomarker for the diagnosis of
ADHD,20,57,58 for treatment efficacy,20,60 and associated with
symptoms of inattentivenesss.59 ... With regard to zinc
supplementation, a placebo controlled trial reported that doses up to
30 mg/day of zinc were safe for at least 8 weeks, but the clinical
effect was equivocal except for the finding of a 37% reduction in
amphetamine optimal dose with 30 mg per day of zinc.110
* ^ Paulos MA, Tessel RE (February 1982). "
beta-phenethylamine is elevated in humans after profound stress".
Science. 215 (4536): 1127–1129. PMID 7063846 . The urinary excretion
rate of the endogenous, amphetamine-like substance beta-phenethylamine
was markedly elevated in human subjects in association with an initial
parachuting experience. The increases were delayed in most subjects
and were not correlated with changes in urinary pH or creatinine
* ^ A B C D Szabo A, Billett E, Turner J (2001). "Phenylethylamine,
a possible link to the antidepressant effects of exercise?" . Br J
Sports Med. 35 (5): 342–343. PMC 1724404 . PMID 11579070 . doi
:10.1136/bjsm.35.5.342 . The 24 hour mean urinary concentration of
phenylacetic acid was increased by 77% after exercise. ... These
results show substantial increases in urinary phenylacetic acid levels
24 hours after moderate to high intensity aerobic exercise. As
phenylacetic acid reflects phenylethylamine levels3, and the latter
has antidepressant effects, the antidepressant effects of exercise
appear to be linked to increased phenylethylamine concentrations.
Furthermore, considering the structural and pharmacological analogy
between amphetamines and phenylethylamine, it is conceivable that
phenylethylamine plays a role in the commonly reported "runners high"
thought to be linked to cerebral β-endorphin activity. The
substantial increase in phenylacetic acid excretion in this study
implies that phenylethylamine levels are affected by exercise. ... A
30 minute bout of moderate to high intensity aerobic exercise
increases phenylacetic acid levels in healthy regularly exercising
men. The findings may be linked to the antidepressant effects of
* ^ A B C D Berry MD (2007). "The potential of trace amines and
their receptors for treating neurological and psychiatric diseases".
Rev Recent Clin Trials. 2 (1): 3–19. PMID 18473983 . doi
:10.2174/157488707779318107 . It has also been suggested that the
antidepressant effects of exercise are due to an exercise-induced
elevation of PE .
* ^ A B C Broadley KJ (March 2010). "The vascular effects of trace
amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. PMID
19948186 . doi :10.1016/j.pharmthera.2009.11.005 . Trace amines are
metabolized in the mammalian body via monoamine oxidase (MAO; EC
18.104.22.168) (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
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
... * ^ "2-PHENYLETHYLAMINE". United States National Library of
Medicine – Toxicology Data Network. Hazardous Substances Data Bank.
Retrieved 20 September 2016.
* ^ A B Wimalasena K (July 2011). "Vesicular monoamine
transporters: structure-function, pharmacology, and medicinal
chemistry" . Med Res Rev. 31 (4): 483–519. PMC 3019297 . PMID
20135628 . doi :10.1002/med.20187 . Phenylethylamine (10), amphetamine
, methylenedioxy methamphetamine and N-methyl-4-phenylpyridinium (15)
are all more potent inhibitors of VMAT2...
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1996). "Distinct pharmacological properties and distribution in
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* ^ Offermanns, S; Rosenthal, W, eds. (2008). Encyclopedia of
Molecular Pharmacology (2nd ed.). Berlin: Springer. pp. 1219–1222.
ISBN 3540389164 .
* ^ A B C D 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. PMC 3005101 . PMID 21073468 . doi
* ^ A B C D Gozal EA, O'Neill BE, Sawchuk MA, Zhu H, Halder M, Chou
CC, Hochman S (2014). "Anatomical and functional evidence for trace
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spinal cord" . Front Neural Circuits. 8: 134. PMC 4224135 . PMID
25426030 . doi :10.3389/fncir.2014.00134 .
TAAR1 activity appears to
depress monoamine transport and limit dopaminergic and serotonergic
neuronal firing rates via interactions with presynaptic D2 and 5-HT1A
autoreceptors, respectively (Wolinsky et al., 2007; Lindemann et al.,
2008; Xie and Miller, 2008; Xie et al., 2008; Bradaia et al., 2009;
Revel et al., 2011; Leo et al., 2014). ...
TAAR1 and TAAR4 labeling in
all neurons appeared intracellular, consistent with previous reported
TAAR1 (Miller, 2011). A cytoplasmic location of ligand and
receptor (e.g., tyramine and TAAR1) supports intracellular activation
of signal transduction pathways, as suggested previously (Miller,
2011). ... Additionally, once transported intracellularly, they could
act on presynaptic TAARs to alter basal activity (Miller, 2011). ...
As reported for
TAAR1 in HEK cells (Bunzow et al., 2001; Miller,
2011), we observed cytoplasmic labeling for
TAAR1 and TAAR4, both of
which are activated by the TAs (Borowsky et al., 2001). A cytoplasmic
location of the ligand and the receptor (e.g., tyramine and TAAR1)
would support intracellular activation of signal transduction pathways
(Miller, 2011). Such a co-localization would not require release from
vesicles and could explain why the TAs do not appear to be found there
(Berry, 2004; Burchett and Hicks, 2006).
* ^ Deepak N, Sara T, Andrew H, Darrell DM, Glen BB (2011). "Trace
amines and their relevance to psychiatry and neurology: a brief
overview". Bulletin of Clinical Psychopharmacology. 21 (1): 73–79.
doi :10.5350/KPB-BCP201121113 . Interestingly, PEA can also stimulate
acetylcholine release through activation of glutamatergic signaling
pathways (21), and PEA and p-TA have been reported to depress GABAB
receptor-mediated responses in dopaminergic neurons (22,23). Although
PEA, T and p-TA have been reported to be present in synaptosomes
(nerve ending preparations isolated during homogenization and
centrifugation of brain tissue) (24), research with reserpine and
neurotoxins suggests that m- and p-TA may be stored in vesicles while
PEA and T are not (25-27). ... the antidepressant effects of exercise
have been suggested to be due to an elevation of PEA (57). l-Deprenyl
(selegiline), a selective inhibitor of MAO-B, is used in the treatment
of Parkinson’s disease and produces a marked increase in brain
levels of PEA relative to other amines (20,58). ... Interestingly, the
gene for aromatic amino acid decarboxylase (AADC), the major enzyme
involved in the synthesis of the trace amines, is located in the same
region of chromosome 7 that has been proposed as a susceptibility
locus for ADHD (50)
* ^ Khan MZ, Nawaz W (October 2016). "The emerging roles of human
trace amines and human trace amine-associated receptors (hTAARs) in
central nervous system". Biomed. Pharmacother. 83: 439–449. PMID
27424325 . doi :10.1016/j.biopha.2016.07.002 .
* ^ Broadley KJ (March 2010). "The vascular effects of trace amines
and amphetamines". Pharmacol. Ther. 125 (3): 363–375. PMID 19948186
. doi :10.1016/j.pharmthera.2009.11.005 .
* ^ Lindemann L, Hoener MC (May 2005). "A renaissance in trace
amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26
(5): 274–281. PMID 15860375 . doi :10.1016/j.tips.2005.03.007 .
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24374199 . doi :10.1016/j.ejphar.2013.12.025 . The highest level of
brain CYP2D activity was found in the substantia nigra ... The in
vitro and in vivo studies have shown the contribution of the
alternative CYP2D-mediated dopamine synthesis to the concentration of
this neurotransmitter although the classic biosynthetic route to
dopamine from tyrosine is active. ...
Tyramine levels are especially
high in the basal ganglia and limbic system, which are thought to be
related to individual behavior and emotion (Yu et al., 2003c). ... Rat
CYP2D isoforms (2D2/2D4/2D18) are less efficient than human
the generation of dopamine from p-tyramine. The Km values of the CYP2D
isoforms are as follows:
CYP2D6 (87–121 μm) ≈ CYP2D2 ≈ CYP2D18
> CYP2D4 (256 μm) for m-tyramine and CYP2D4 (433 μm) > CYP2D2 ≈
CYP2D6 > CYP2D18 (688 μm) for p-tyramine
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N-hydroxy metabolite, followed by a rapid second oxygenation to
produce the trans-oximes (Lin the Km is between 90 and 200 μM (Lin &
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PMID 361043 . doi :10.1016/0006-2952(78)90543-9 .
Phenethylamine MS Spectrum