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 L-phenylalanine
by 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, in orally ingested phenethylamine, a
significant amount is metabolized in the small intestine by monoamine
oxidase B (MAO-B) and then aldehyde dehydrogenase (ALDH), which
convert it to phenylacetic acid. This means that for significant
concentrations to reach the brain, the dosage must be higher than for
other methods of administration.
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, anorectics,
bronchodilators, decongestants, and/or antidepressants, among others.
1 Natural occurrence
2.1 Substituted derivatives
2.3 Detection in body fluids
4 See also
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: Lactobacillus,
Clostridium, 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.
PEA powder and crystals
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 odor, 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.
Phenethylamine is 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.
Main article: Substituted phenethylamine
Substituted phenethylamines are a chemical class of organic compounds
that are based upon the phenethylamine structure;[note 1] 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 as MDMA
(ecstasy), methamphetamine, and cathinones, are also members of the
class. All of the substituted amphetamines are phenethylamines as
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.
Electrosynthesis of 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
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
This section needs expansion with: . You can help by adding to it.
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 from
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
This section needs expansion with: . You can help by adding to
it. (September 2016)
Phenethylamine pharmacodynamics in a TAAR1–dopamine neuron
v · t · e
Both amphetamine and phenethylamine induce neurotransmitter release
from VMAT2 and bind to TAAR1. 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
Phenethylamine, being similar to amphetamine in its action at their
common biomolecular targets, releases norepinephrine and
Phenethylamine also appears to induce
acetylcholine release via a glutamate-mediated mechanism.
Phenethylamine has been shown to bind to two human trace
amine-associated receptors, h
TAAR1 and hTAAR2, as an agonist.
Biosynthetic pathways for catecholamines and trace amines in the human
In humans, catecholamines and phenethylaminergic trace amines are
derived from the amino acid L-phenylalanine.
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), the semicarbazide-sensitive amine
AOC2 and AOC3, 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.
Phenylacetic acid is the primary urinary metabolite of
phenethylamine and is produced via monoamine oxidase metabolism and
subsequent aldehyde dehydrogenase metabolism.
the intermediate product which is produced by monoamine oxidase and
then further metabolized into β-phenylacetic acid by aldehyde
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.
doi:10.3389/fnins.2016.00148. PMC 4820462 . PMID 27092049.
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.,
^ a b c 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.
doi:10.1016/j.biopha.2016.07.002. PMID 27424325.
^ a b c d e f g h i j k l m Lindemann L, Hoener MC (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. 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 [52,53], 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 [18,55].
^ a b c d e f g h i 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
184.108.40.206) (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
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
^ a b c d e f g h i j k l m n o "Phenylethylamine". HMDB
Version 3.6. Human Metabolome Database. 11 February 2016.
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^ a b c 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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^ a b Kaitaniemi, S; Elovaara, H; Grön, K; Kidron, H; Liukkonen, J;
Salminen, T; Salmi, M; Jalkanen, S; Elima, K (2009). "The unique
substrate specificity of human AOC2, a semicarbazide-sensitive amine
oxidase". Cell. Mol. Life Sci. 66 (16): 2743–57.
doi:10.1007/s00018-009-0076-5. PMID 19588076. The preferred in
vitro substrates of
AOC2 were found to be 2-phenylethylamine,
tryptamine and p-tyramine instead of methylamine and benzylamine, the
favored substrates of AOC3.
^ a b Krueger SK, Williams DE; Williams (June 2005). "Mammalian
flavin-containing monooxygenases: structure/function, genetic
polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3):
357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602 .
PMID 15922018. The biogenic amines, phenethylamine and tyramine,
are N-oxygenated by FMO to produce the N-hydroxy metabolite, followed
by a rapid second oxygenation to produce the trans-oximes (Lin &
Cashman, 1997a, 1997b). This stereoselective N-oxygenation to the
trans-oxime is also seen in the FMO-dependent N-oxygenation of
amphetamine (Cashman et al., 1999) ... Interestingly, FMO2, which
very efficiently N-oxygenates N-dodecylamine, is a poor catalyst of
phenethylamine N-oxygenation. The most efficient human FMO in
phenethylamine N-oxygenation is FMO3, the major FMO present in adult
human liver; the Km is between 90 and 200 μM (Lin & Cashman,
^ a b Robinson-Cohen C, Newitt R, Shen DD, Rettie AE, Kestenbaum BR,
Himmelfarb J, Yeung CK (August 2016). "Association of FMO3 Variants
Trimethylamine N-Oxide Concentration, Disease Progression, and
Mortality in CKD Patients". PLoS ONE. 11 (8): e0161074.
doi:10.1371/journal.pone.0161074. PMC 4981377 .
PMID 27513517. TMAO is generated from trimethylamine (TMA) via
metabolism by hepatic flavin-containing monooxygenase isoform 3
(FMO3). ... FMO3 catalyzes the oxidation of catecholamine or
catecholamine-releasing vasopressors, including tyramine,
phenylethylamine, adrenaline, and noradrenaline [32, 33].
^ a b "Pharmacology and Biochemistry". Phenethylamine. PubChem
Compound. United States National Library of Medicine – National
Center for Biotechnology Information. Retrieved 28 December 2016.
PLASMA PHARMACOKINETICS OF PEA COULD BE DESCRIBED BY 1ST-ORDER
KINETICS WITH ESTIMATED T/2 OF APPROX 5-10 MIN.
^ a b c "Chemical and Physical Properties". Phenethylamine. PubChem
Compound. United States National Library of Medicine – National
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^ 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.
doi:10.1111/j.1471-4159.2004.02501.x. PMID 15228583.
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(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
^ 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.
doi:10.1016/j.meatsci.2013.06.030. PMID 23896151. 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
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"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. 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.
^ Gary A. Molander; Fabricio Vargas (2007-01-18).
"β-Aminoethyltrifluoroborates: Efficient Aminoethylations via
Suzuki-Miyaura Cross-Coupling". Org. Lett. 9 (2): 203–206.
doi:10.1021/ol062610v. PMC 2593899 . PMID 17217265.
^ 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. doi:10.1016/j.jaac.2012.08.015.
PMID 23021477. 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. doi:10.1126/science.7063846.
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 excretion.
^ 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. doi:10.1136/bjsm.35.5.342.
PMC 1724404 . PMID 11579070. 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 exercise.
^ 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. doi:10.2174/157488707779318107.
PMID 18473983. It has also been suggested that the antidepressant
effects of exercise are due to an exercise-induced elevation of PE
^ "2-PHENYLETHYLAMINE". United States National Library of
Medicine – Toxicology Data Network. Hazardous Substances Data
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structure-function, pharmacology, and medicinal chemistry". Med Res
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PMID 20135628. Phenylethylamine (10), amphetamine [AMPH (11 &
12)], methylenedioxy methamphetamine [METH (13)] and
N-methyl-4-phenylpyridinium (15) are all more potent inhibitors of
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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 results for
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
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,
^ 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)
^ 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.
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Phenethylamine MS Spectrum
Mixed amphetamine salts
TAAR1 (full agonist)
CART (mRNA inducer)
5-HT1A receptor (low affinity ligand)
MAO (weak competitive inhibitor)
Doping in sport
History and culture of substituted amphetamines
History of Benzedrine
Neurobiological effects of physical exercise § Attention deficit
Recreational drug use
Major excitatory/inhibitory systems: Glutamate system: Agmatine
Aspartic acid (aspartate)
Glutamic acid (glutamate)
Serine; GABA system: GABA
Glycine system: α-Alanine
Taurine; GHB system: GHB
Biogenic amines: Monoamines: 6-OHM
Serotonin (5-HT); Trace amines: 3-Iodothyronamine
p-Tyramine; Others: Histamine
Neuropeptides: See here instead.
2-AGE (noladin ether)
Neurosteroids: See here instead.
Adenosine system: Adenosine
Cholinergic system: Acetylcholine
Carbon monoxide (CO)
Hydrogen sulfide (H2S)
Nitric oxide (NO); Candidates: Acetaldehyde
Carbonyl sulfide (COS)
Nitrous oxide (N2O)
Sulfur dioxide (SO2)
Monoamine releasing agents
Selegiline (also D-Deprenyl)
Monoamine activity enhancers: BPAP
DAT modulators: Agonist-like: SoRI-9804
SoRI-20040; Antagonist-like: SoRI-20041
Adrenergic release blockers: Bethanidine
See also: Receptor/signaling modulators •
inhibitors • Adrenergics • Dopaminergics • Serotonergics •
Monoamine metabolism modulators •
Human trace amine-associated receptor ligands
Classical monoamine neurotransmitters
† References for all endogenous human
TAAR1 ligands are provided at
List of trace amines
‡ References for synthetic
TAAR1 agonists can be found at
in the associated compound articles. For
TAAR5 agonists and
inverse agonists, see TAAR for references.
See also: Receptor/signaling modulators
Drugs from PiHKAL