Phenethylamine: Difference between revisions

{{Short description|Organic compound, a stimulant in humans}}

{{Distinguish|1-phenylethylamine|phenylalanine}}

{{about|a specific substance|the class of substances|substituted phenethylamine}}

{{Use dmy dates|date=August 2018}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| Watchedfields =

| Verifiedfields =

| verifiedrevid = 612854585

| IUPAC_name = 2-Phenylethan-1-amine

| image = Phenethylamine2DCSD.svg

| alt = Image of the phenethylamine skeleton

| width = 200

| image2 = Phenethylamine-3D-balls.png

| alt2 = Ball-and-stick model of phenethylamine

| width2 = 200

<!--Clinical data-->| pronounce = {{IPAc-en|f|ɛ|n|'|ɛ|θ|ə|l|ə|m|i:|n}}

| routes_of_administration = [[Oral administration|Oral]] (taken by mouth)

| dependency_liability = [[Psychological dependence|Psychological]]: low–moderate{{citation needed|date=August 2020}}<br />[[Physical dependence|Physical]]: none

| addiction_liability = None–Low (w/o an [[Monoamine oxidase inhibitor#List of MAO inhibiting drugs|MAO-B inhibitor]])<ref name="TAAR1 and TA pharmacology 2016 review">{{cite journal | vauthors = Pei Y, Asif-Malik A, Canales JJ | title = Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications | journal = Frontiers in Neuroscience | volume = 10 | pages = 148 | date = April 2016 | pmid = 27092049 | pmc = 4820462 | doi = 10.3389/fnins.2016.00148 | quote = 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, 2021), 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). | doi-access = free }}</ref><br />Moderate (with an MAO-B inhibitor)<ref name="TAAR1 and TA pharmacology 2016 review"/>

<!--Pharmacokinetic data-->| metabolism = Primarily: [[Monoamine oxidase B|MAO-B]]<ref name="Renaissance"/><ref name="Vascular"/><ref name="HMDB PEA"/><br />Other enzymes: [[Monoamine oxidase A|MAO-A]],<ref name="HMDB PEA"/><ref name="PEA_MAO-A_and_B_Substrate-Suzuki"/> [[semicarbazide-sensitive amine oxidase|SSAO]]s ([[AOC2]] & [[AOC3]]),<ref name="HMDB PEA"/><ref name="SSAO"/> [[Phenylethanolamine N-methyltransferase|PNMT]],<ref name="Renaissance"/><ref name="Vascular"/><ref name="HMDB PEA"/> [[Aralkylamine N-acetyltransferase|AANAT]],<ref name="HMDB PEA"/> [[flavin-containing monooxygenase 3|FMO3]],<ref name="FMO"/><ref name="FMO3 catecholamines"/> and others

| class = {{abbrlink|CNS|central nervous system}} [[stimulant]], [[anorectic]]

<!--Physiological data-->| source_tissues = [[Substantia nigra pars compacta]];<br />[[Ventral tegmental area]];<br />[[Locus coeruleus]];<br />many others

| target_tissues = System-wide

| receptors = Varies greatly across species;<br />Human receptors: [[hTAAR1]]<ref name="Human trace amines and hTAARs October 2016 review"/>

| precursor = [[L-Phenylalanine]]<ref name="Renaissance"/><ref name="Vascular"/>

| biosynthesis = [[Aromatic L-amino acid decarboxylase]] (AADC)<ref name="Renaissance"/><ref name="Vascular"/>

| synonyms = PEA; phenylethylamine, phetamine

<!--Legal status-->| legal_AU = Unscheduled

| legal_CA = Unscheduled

| legal_NZ = Unscheduled

| legal_UK = Unscheduled

| legal_UN = Unscheduled

| legal_US = Unscheduled

<!--Pharmacokinetic data-->| elimination_half-life = {{ubl |Exogenous: 5–10 minutes<ref name="Pubchem exogenous half-life"/> |Endogenous: ~30 seconds<ref name="Renaissance"/>}}

| excretion = [[Renal]] (kidneys)

<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 64-04-0

| PubChem = 1001

| IUPHAR_ligand = 2144

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB04325

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = C05332

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 13856352

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 327C7L2BXQ

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 18397

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 610

| NIAID_ChemDB = 018561

| ATC_prefix = none

| ATC_suffix = <!--Chemical data-->

| C = 8

| H = 11

| N = 1

| smiles = NCCc1ccccc1

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C8H11N/c9-7-6-8-4-2-1-3-5-8/h1-5H,6-7,9H2

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = BHHGXPLMPWCGHP-UHFFFAOYSA-N

<!--Physical data-->| boiling_point = 195

| boiling_notes = <ref name="Pubchem">{{cite encyclopedia|title=Phenethylamine|section-url=https://pubchem.ncbi.nlm.nih.gov/compound/1001?from=summary#section=Chemical-and-Physical-Properties|section=Chemical and Physical Properties |encyclopedia=PubChem Compound |publisher = United States National Library of Medicine&nbsp;– National Center for Biotechnology Information}}</ref>

| melting_point = -60

| melting_notes = <ref name="Pubchem"/>

| density = 0.9640 <!--Pubchem-->

}}

'''Phenethylamine'''{{#tag:ref|Synonyms and alternate spellings include: '''phenylethylamine''', '''β-phenylethylamine''' ({{nowrap|'''β-PEA'''}}), '''2-phenylethylamine''', '''{{nowrap|1-amino-2-phenylethane}}''', and '''{{nowrap|2-phenylethan-1-amine}}'''.|group= "note"}} ('''PEA''') is an [[organic compound]], [[natural product|natural]] [[monoamine]] [[alkaloid]], and [[trace amine]], which acts as a [[central nervous system]] [[stimulant]] in humans. In the brain, phenethylamine regulates [[monoamine neurotransmitter|monoamine neurotransmission]] by binding to [[trace amine-associated receptor 1]] (TAAR1) and inhibiting [[vesicular monoamine transporter 2]] (VMAT2) in monoamine [[neuron]]s.<ref name="TAAR1 and TA pharmacology 2016 review" /><ref name="PEA VMAT2 MEDRS review" /><ref name="Miller" /> To a lesser extent, it also acts as a [[neurotransmitter]] in the human [[central nervous system]].<ref name="PEA 2">{{cite journal | vauthors = Sabelli HC, Mosnaim AD, Vazquez AJ, Giardina WJ, Borison RL, Pedemonte WA | title = Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle | journal = Biological Psychiatry | volume = 11 | issue = 4 | pages = 481–524 | date = August 1976 | pmid = 9160 | doi = }}</ref> In mammals, phenethylamine [[biosynthesis|is produced]] from the [[amino acid]] [[L-phenylalanine]] by the enzyme [[aromatic L-amino acid decarboxylase]] via [[enzymatic]] [[decarboxylation]].<ref name="Berry_2004">{{cite journal | vauthors = Berry MD | title = Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators | journal = Journal of Neurochemistry | volume = 90 | issue = 2 | pages = 257–271 | date = July 2004 | pmid = 15228583 | doi = 10.1111/j.1471-4159.2004.02501.x | doi-access = free }}</ref> In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as [[chocolate]], especially after [[microorganism|microbial]] [[fermentation (food)|fermentation]].

Phenethylamine is sold as a [[dietary supplement]] for purported [[Mood (psychology)|mood]] and [[weight loss]]-related [[therapeutic benefit]]s; however, in [[oral administration|orally]] ingested phenethylamine, a significant amount is metabolized in the [[small intestine]] by [[monoamine oxidase B]] (MAO-B) and then [[aldehyde dehydrogenase]] (ALDH), which converts it to [[phenylacetic acid]].<ref name="HMDB PEA">{{cite HMDB |title=Showing metabocard for Phenylethylamine (HMDB0012275) |author1-link=David S. Wishart |url=https://hmdb.ca/metabolites/HMDB0012275}}</ref> This means that for significant [[concentration]]s to reach the [[brain]], the dosage must be higher than for other methods of administration.<ref name="HMDB PEA"/><ref name="PEA_MAO-A_and_B_Substrate-Suzuki">{{cite journal | vauthors = Suzuki O, Katsumata Y, Oya M | title = Oxidation of beta-phenylethylamine by both types of monoamine oxidase: examination of enzymes in brain and liver mitochondria of eight species | journal = Journal of Neurochemistry | volume = 36 | issue = 3 | pages = 1298–1301 | date = March 1981 | pmid = 7205271 | doi = 10.1111/j.1471-4159.1981.tb01734.x | s2cid = 36099388 }}</ref><ref name="PEA_MAO-B_Substrate-Yang">{{cite journal | vauthors = Yang HY, Neff NH | title = Beta-phenylethylamine: a specific substrate for type B monoamine oxidase of brain | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 187 | issue = 2 | pages = 365–371 | date = November 1973 | pmid = 4748552 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=4748552 }}</ref> Some authors postulated its role in people's falling-in-love without substantiating it with any direct evidence.<ref>{{Cite journal| vauthors = Godfrey PD, Hatherley LD, Brown RD |date=1995-08-01|title=The Shapes of Neurotransmitters by Millimeter-Wave Spectroscopy: 2-Phenylethylamine|url=https://doi.org/10.1021/ja00136a019|journal=Journal of the American Chemical Society|volume=117|issue=31|pages=8204–8210|doi=10.1021/ja00136a019|issn=0002-7863}}</ref><ref>{{cite journal | vauthors = Marazziti D, Canale D | title = Hormonal changes when falling in love | journal = Psychoneuroendocrinology | volume = 29 | issue = 7 | pages = 931–936 | date = August 2004 | pmid = 15177709 | doi = 10.1016/j.psyneuen.2003.08.006 | s2cid = 24651931 }}</ref>

Phenethylamines, or more properly, [[substituted phenethylamine]]s, are the group of phenethylamine [[Derivative (chemistry)|derivatives]] that contain phenethylamine as a "backbone"; in other words, this [[Chemical classification|chemical class]] includes [[derivative (chemistry)|derivative]] compounds that are formed by replacing one or more hydrogen atoms in the phenethylamine core structure with [[substituent]]s. The class of [[substituted phenethylamine]]s includes all [[substituted amphetamine]]s, and [[substituted methylenedioxyphenethylamine]]s (MDxx), and contains many drugs which act as [[Empathogen-entactogen|empathogen]]s, [[stimulant]]s, [[psychedelic drug|psychedelics]], [[anorectic]]s, [[bronchodilator]]s, [[decongestant]]s, and/or [[antidepressant]]s, among others.

==Natural occurrence==

Phenethylamine is produced by a wide range of species throughout the plant and animal kingdoms, including humans;<ref name="Berry_2004" /><ref>{{cite journal |doi=10.1016/0031-9422(77)83004-5 |title=Phenethylamine and related compounds in plants |year=1977 | vauthors = Smith TA |journal=Phytochemistry |volume=16 |issue=1 |pages=9–18|bibcode=1977PChem..16....9S }}</ref> it is also produced by certain [[fungi]] and [[bacteria]] (genera: ''[[Lactobacillus]], [[Clostridium]], [[Pseudomonas]]'' and the family [[Enterobacteriaceae]]) and acts as a potent [[antimicrobial]] against certain pathogenic strains of ''[[Escherichia coli]]'' (e.g., the [[Escherichia coli O157:H7|O157:H7 strain]]) at sufficient concentrations.<ref name="pmid23896151">{{cite journal | vauthors = Lynnes T, Horne SM, Prüß BM | title = β-Phenylethylamine as a novel nutrient treatment to reduce bacterial contamination due to Escherichia coli O157:H7 on beef meat | journal = Meat Science | volume = 96 | issue = 1 | pages = 165–171 | date = January 2014 | pmid = 23896151 | doi = 10.1016/j.meatsci.2013.06.030 | quote = 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. }}</ref>

==Chemistry==

{{multiple image

|direction= vertical

|align = right

|image1 = PEA powder.jpg

|width1 = 220

|image2 = PEA crystals.jpg

|width2 = 220

|caption2= 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]].<ref name="PubChem PEA"/> It is a colourless liquid at room temperature that has a fishy odor, and is soluble in water, [[ethanol]] and [[diethyl ether|ether]].<ref name="PubChem PEA"/> Its density is 0.964 g/ml and its boiling point is 195&nbsp;°C.<ref name="Pubchem"/> Upon exposure to air, it combines with [[carbon dioxide]] to form a solid [[carbonate]] [[salt (chemistry)|salt]].<ref name=Merck>{{cite book | veditors = O'Neil MJ | title = The Merck Index – An Encyclopedia of Chemicals, Drugs, and Biologicals. | edition = 13th | location = Whitehouse Station, NJ | publisher = Merck and Co., Inc. | date = 2001 | page = 1296 }}</ref> Phenethylamine is strongly [[base (chemistry)|basic]], pK_b = 4.17 (or pK_a = 9.83), as measured using the HCl salt, and forms a stable crystalline [[hydrochloride]] salt with a melting point of 217&nbsp;°C.<ref name="PubChem PEA"/><ref>{{cite journal |doi=10.1021/ja01150a055 |title=Dissociation Constants of Adrenergic Amines |year=1951 | vauthors = Leffler EB, Spencer HM, Burger A |journal=Journal of the American Chemical Society |volume=73 |issue=6 |pages=2611–3}}</ref>

===Substituted derivatives===

{{Main|Substituted phenethylamine}}

Substituted phenethylamines are a [[chemical class]] of [[organic compound]]s based upon the phenethylamine structure;{{#tag:ref|In other words, all of the compounds that belong to this class are [[structural analog#Chemistry|structural analogs]] of phenethylamine.|group="note"}} the class is composed of all the [[derivative (chemistry)|derivative]] compounds of phenethylamine which can be formed by replacing, or [[substitution reaction|substituting]], one or more [[hydrogen atom]]s in the phenethylamine core structure with [[substituent]]s.

Many substituted phenethylamines are psychoactive drugs, which belong to a variety of different drug classes, including [[central nervous system stimulant]]s (e.g., [[amphetamine]]), [[hallucinogen]]s (e.g., [[2,5-dimethoxy-4-methylamphetamine]]), [[entactogen]]s (e.g., [[3,4-methylenedioxyamphetamine]]), [[appetite suppressant]]s (e.g. [[phentermine]]), [[nasal decongestant]]s and [[bronchodilator]]s (e.g., [[pseudoephedrine]]), [[antidepressant]]s (e.g. [[bupropion]]), [[Management of Parkinson's disease#Medication|antiparkinson agent]]s (e.g., [[selegiline]]), and [[vasopressor]]s (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 [[hormone]]s, monoamine neurotransmitters, and many [[trace amine]]s (e.g., [[dopamine]], [[norepinephrine]], [[adrenaline]], [[tyramine]], and others) – are substituted phenethylamines. Dopamine

is simply phenethylamine with a hydroxyl group attached to the 3 and 4 position of the benzene ring. Several notable recreational drugs, such as [[MDMA]] (ecstasy), [[methamphetamine]], and [[cathinone]]s, are also members of the class. All of the [[substituted amphetamine]]s are phenethylamines, as well.

Pharmaceutical drugs that are substituted phenethylamines include [[phenelzine]], [[phenformin]], and [[fanetizole]], among many others.

===Synthesis===

One method for preparing β-phenethylamine, set forth in J. C. Robinson 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&nbsp;°C and a pressure of 13.8 MPa. Alternative syntheses are outlined in the footnotes to this preparation.<ref>{{cite journal | vauthors = Robinson JC, Snyder HR |year=1955 |title=β-Phenylethylamine |url=http://www.orgsyn.org/Content/pdfs/procedures/CV3P0720.pdf |journal=Organic Syntheses, Collected Volume |volume=3 |page=720}}</ref>

A much more convenient method for the synthesis of β-phenethylamine is the reduction of [[Beta-Nitrostyrene|ω-nitrostyrene]] by [[lithium aluminium hydride]] in ether, whose successful execution was first reported by R. F. Nystrom and W. G. Brown in 1948.<ref>{{cite journal | vauthors = Nystrom RF, Brown WG | title = Reduction of organic compounds by lithium aluminum hydride; halides, quinones, miscellaneous nitrogen compounds | journal = Journal of the American Chemical Society | volume = 70 | issue = 11 | pages = 3738–3740 | date = November 1948 | pmid = 18102934 | doi = 10.1021/ja01191a057 }}</ref>

Phenethylamine can also be produced via the cathodic reduction of [[benzyl cyanide]] in a divided cell.<ref name="Shamelessly stolen from the Electrosynthesis article">{{cite journal| vauthors = Krishnan V, Muthukumaran A, Udupa HV |title=The electroreduction of benzyl cyanide on iron and cobalt cathodes|journal=Journal of Applied Electrochemistry|year=1979|volume=9|issue=5|pages=657–659|doi=10.1007/BF00610957|s2cid=96102382 }}</ref>

[[File:Benzyl cyanide electrolytic reduction.png|450px|center|[[Electrosynthesis]] of phenethylamine from [[benzyl cyanide]]<ref name="Shamelessly stolen from the Electrosynthesis article"/>|thumb]]

Assembling phenethylamine structures for synthesis of compounds such as epinephrine, amphetamines, tyrosine, and dopamine by adding the beta-aminoethyl side chain to the [[phenyl]] ring is possible. This can be done via [[Friedel-Crafts acylation]] with N-protected [[acyl chloride]]s when the arene is activated, or by [[Heck reaction]] of the phenyl with N-vinyl[[oxazolone]], 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 cross-coupling]].<ref>{{cite journal | vauthors = Molander GA, Vargas F | title = Beta-aminoethyltrifluoroborates: efficient aminoethylations via Suzuki-Miyaura cross-coupling | journal = Organic Letters | volume = 9 | issue = 2 | pages = 203–206 | date = January 2007 | pmid = 17217265 | pmc = 2593899 | doi = 10.1021/ol062610v }}</ref>

===Detection in body fluids===

{{Expand section|<ref name="HMDB PEA"/>|date=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.<ref name="Zinc and PEA"/> In treatment-responsive individuals, amphetamine and [[methylphenidate]] greatly increase urinary phenethylamine concentration.<ref name="Zinc and PEA">{{cite journal | vauthors = Scassellati C, Bonvicini C, Faraone SV, Gennarelli M | title = Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 51 | issue = 10 | pages = 1003–1019.e20 | date = October 2012 | pmid = 23021477 | doi = 10.1016/j.jaac.2012.08.015 | quote = Although we did not find a sufficient number of studies suitable for a meta-analysis of PEA and ADHD, three studies^20,57,58 confirmed that urinary levels of PEA were significantly lower in patients with ADHD compared with controls.&nbsp;... Administration of D-amphetamine and methylphenidate resulted in a markedly increased urinary excretion of PEA,^20,60 suggesting that ADHD treatments normalize PEA levels.&nbsp;... 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&nbsp;... With regard to zinc supplementation, a placebo controlled trial reported that doses up to 30&nbsp;mg/day of zinc were safe for at least 8&nbsp;weeks, but the clinical effect was equivocal except for the finding of a 37%&nbsp;reduction in amphetamine optimal dose with 30&nbsp;mg per day of zinc.¹¹⁰ }}</ref> An ADHD [[Biomarker (medicine)|biomarker]] review also indicated that urinary phenethylamine levels could be a diagnostic biomarker for ADHD.<ref name="Zinc and PEA"/>

Thirty minutes of moderate- to high-intensity physical exercise has been shown to induce an increase in urinary [[phenylacetic acid]], the primary metabolite of phenethylamine.<ref name="Renaissance">{{cite journal | vauthors = Lindemann L, Hoener MC | title = A renaissance in trace amines inspired by a novel GPCR family | journal = Trends in Pharmacological Sciences | volume = 26 | issue = 5 | pages = 274–281 | date = May 2005 | pmid = 15860375 | doi = 10.1016/j.tips.2005.03.007 | quote = The pharmacology of TAs might also contribute to a molecular understanding of the well-recognized antidepressant effect of physical exercise [51]. 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 [54], which mirrors increased β-PEA synthesis in view of its limited endogenous pool half-life of ~30 s [18,55]. }}</ref><ref name="PEA exercise primary">{{cite journal | vauthors = Szabo A, Billett E, Turner J | title = Phenylethylamine, a possible link to the antidepressant effects of exercise? | journal = British Journal of Sports Medicine | volume = 35 | issue = 5 | pages = 342–343 | date = October 2001 | pmid = 11579070 | pmc = 1724404 | doi = 10.1136/bjsm.35.5.342 | quote = The 24 hour mean urinary concentration of phenylacetic acid was increased by 77% after exercise.&nbsp;... 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.&nbsp;... 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. }}</ref><ref name="Neuropsychiatric">{{cite journal | vauthors = Berry MD | title = The potential of trace amines and their receptors for treating neurological and psychiatric diseases | journal = Reviews on Recent Clinical Trials | volume = 2 | issue = 1 | pages = 3–19 | date = January 2007 | pmid = 18473983 | doi = 10.2174/157488707779318107 | quote = It has also been suggested that the antidepressant effects of exercise are due to an exercise-induced elevation of PE [151]. | citeseerx = 10.1.1.329.563 }}</ref> Two reviews noted a study where the mean 24&nbsp;hour urinary phenylacetic acid concentration following just 30&nbsp;minutes of intense exercise rose 77% above its base level;<ref name="Renaissance"/><ref name="PEA exercise primary"/><ref name="Neuropsychiatric"/> 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&nbsp;seconds.<ref name="Renaissance"/><ref name="PEA exercise primary"/><ref name="Neuropsychiatric"/><ref name="Vascular"/> In a resting state, phenethylamine is synthesized in [[catecholamine]] neurons from {{smallcaps all|L}}-[[phenylalanine]] by [[aromatic amino acid decarboxylase]] at approximately the same rate as dopamine is produced.<ref name="Vascular">{{cite journal | vauthors = Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacology & Therapeutics | 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 }}</ref> Monoamine oxidase 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 completely deaminated in the gut as it is a selective substrate for MAO-B, which is not primarily 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.<ref name="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. 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 [[euphoria|euphoric]] effects of a [[runner's high]], as both phenethylamine and amphetamine are potent [[euphoriant]]s.<ref name="Renaissance"/><ref name="PEA exercise primary"/><ref name="Neuropsychiatric"/>

[[Skydiving]] has also been shown to induce a marked increase in urinary phenethylamine concentrations.<ref name="PubChem PEA">{{cite encyclopedia |title=Phenethylamine |url=https://pubchem.ncbi.nlm.nih.gov/compound/1001 |encyclopedia=PubChem Compound |publisher= United States National Library of Medicine&nbsp;– National Center for Biotechnology Information |access-date= 28 December 2016}}</ref><ref name="Skydiving">{{cite journal | vauthors = Paulos MA, Tessel RE | title = Excretion of beta-phenethylamine is elevated in humans after profound stress | journal = Science | volume = 215 | issue = 4536 | pages = 1127–1129 | date = February 1982 | pmid = 7063846 | doi = 10.1126/science.7063846 | quote = 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. | bibcode = 1982Sci...215.1127P }}</ref>

{{See also|Neurobiological effects of physical exercise#β-Phenylethylamine}}

{{Expand section|<ref name="PubChem PEA"/><ref name="TOXNET PEA">{{cite encyclopedia |title=2-PHENYLETHYLAMINE |url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@DOCNO+3526 |encyclopedia=United States National Library of Medicine&nbsp;– Toxicology Data Network |publisher=Hazardous Substances Data Bank |access-date=20 September 2016 }}</ref>|date=September 2016}}

===Pharmacodynamics===

{{Amphetamine pharmacodynamics|header=Phenethylamine pharmacodynamics in a TAAR1–dopamine neuron|caption=Both amphetamine and phenethylamine induce neurotransmitter release from [[VMAT2]]<ref name="PEA VMAT2 MEDRS review">{{cite journal | vauthors = Wimalasena K | title = Vesicular monoamine transporters: structure-function, pharmacology, and medicinal chemistry | journal = Medicinal Research Reviews | volume = 31 | issue = 4 | pages = 483–519 | date = July 2011 | pmid = 20135628 | pmc = 3019297 | doi = 10.1002/med.20187 | quote = Phenylethylamine (10), amphetamine [AMPH (11 & 12)], methylenedioxy methamphetamine [METH (13)] and N-methyl-4-phenylpyridinium (15) are all more potent inhibitors of VMAT2... }}</ref><ref name="pmid8643547">{{cite journal | vauthors = Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E | title = Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 10 | pages = 5166–5171 | date = May 1996 | pmid = 8643547 | pmc = 39426 | doi = 10.1073/pnas.93.10.5166 | doi-access = free | bibcode = 1996PNAS...93.5166E }}</ref><ref name="Offermanns">{{cite book |editor1=Offermanns, S |editor2= Rosenthal, W |title=Encyclopedia of Molecular Pharmacology |year=2008|publisher=Springer|location=Berlin|isbn=978-3540389163|pages=1219–1222|edition=2nd}}</ref> and bind to [[TAAR1]].<ref name="Miller">{{cite journal | vauthors = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = Journal of Neurochemistry | volume = 116 | issue = 2 | pages = 164–176 | date = January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref><ref name="Cites Miller 2011 review">{{cite journal | vauthors = Gozal EA, O'Neill BE, Sawchuk MA, Zhu H, Halder M, Chou CC, Hochman S | title = Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord | journal = Frontiers in Neural Circuits | volume = 8 | pages = 134 | year = 2014 | pmid = 25426030 | pmc = 4224135 | doi = 10.3389/fncir.2014.00134 | quote = 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). &nbsp;... 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).&nbsp;... Additionally, once transported intracellularly, they could act on presynaptic TAARs to alter basal activity (Miller, 2011).&nbsp;... 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). | doi-access = free }}</ref> 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.<ref name="Miller"/><ref name="Cites Miller 2011 review"/> Phosphorylated DAT then either operates in reverse or [[endocytosis|withdraws into the axon terminal]] and ceases transport.<ref name="Miller"/><ref name="Cites Miller 2011 review"/>|align=bottom}}

Phenethylamine, being similar to [[amphetamine]] in its action at their common [[biomolecular target]]s, [[releasing agent|releases]] [[norepinephrine]] and [[dopamine]].<ref name="PEA VMAT2 MEDRS review"/><ref name="Miller"/><ref name="Cites Miller 2011 review"/> Phenethylamine also appears to induce acetylcholine release via a glutamate-mediated mechanism.<ref name="TA Neuropsych">{{cite journal |vauthors= Deepak N, Sara T, Andrew H, Darrell DM, Glen BB |title= Trace amines and their relevance to psychiatry and neurology: a brief overview |journal= Bulletin of Clinical Psychopharmacology |volume= 21 |issue= 1 |pages= 73–79 |date= 2011 |doi= 10.5350/KPB-BCP201121113 |quote= 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).&nbsp;... 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).&nbsp;... 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)}}</ref>

Phenethylamine has been shown to bind to [[human trace amine-associated receptor 1]] (hTAAR1) as an [[receptor agonist|agonist]].<ref name="Human trace amines and hTAARs October 2016 review">{{cite journal | vauthors = Khan MZ, Nawaz W | title = The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system | journal = Biomedicine & Pharmacotherapy | volume = 83 | pages = 439–449 | date = October 2016 | pmid = 27424325 | doi = 10.1016/j.biopha.2016.07.002 }}</ref> β-PEA is also an odorant binding TAAR4 in mice thought to mediate predator avoidance.<ref name="Liberles_2015">{{cite journal | vauthors = Liberles SD | title = Trace amine-associated receptors: ligands, neural circuits, and behaviors | journal = Current Opinion in Neurobiology | volume = 34 | issue = | pages = 1–7 | date = October 2015 | pmid = 25616211 | pmc = 4508243 | doi = 10.1016/j.conb.2015.01.001 | url = }}</ref> Unlike its derivative [[epinephrine]] (adrenaline), phenethylamine is inactive as an agonist of the [[alpha-adrenergic receptor|α-]] and [[β-adrenergic receptor]]s.<ref name="PinckaersBlankesteijnMircheva2024">{{cite journal | vauthors = Pinckaers NE, Blankesteijn WM, Mircheva A, Shi X, Opperhuizen A, Schooten FV, Vrolijk MF | title = In Vitro Activation of Human Adrenergic Receptors and Trace Amine-Associated Receptor 1 by Phenethylamine Analogues Present in Food Supplements | journal = Nutrients | volume = 16 | issue = 11 | date = May 2024 | page = 1567 | pmid = 38892500 | pmc = 11174489 | doi = 10.3390/nu16111567 | doi-access = free | url = }}</ref>

Phenethylamine is a [[monoaminergic activity enhancer]] (MAE) of [[serotonin]], [[norepinephrine]], and [[dopamine]] in addition to its catecholamine-releasing activity.<ref name="ShimazuMiklya2004">{{cite journal | vauthors = Shimazu S, Miklya I | title = Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 28 | issue = 3 | pages = 421–427 | date = May 2004 | pmid = 15093948 | doi = 10.1016/j.pnpbp.2003.11.016 | s2cid = 37564231 }}</ref><ref name="Knoll2003">{{cite journal | vauthors = Knoll J | title = Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives | journal = Neurochem Res | volume = 28 | issue = 8 | pages = 1275–1297 | date = August 2003 | pmid = 12834268 | doi = 10.1023/a:1024224311289 | url = }}</ref><ref name="KnollMiklyaKnoll1996">{{cite journal | vauthors = Knoll J, Miklya I, Knoll B, Markó R, Rácz D | title = Phenylethylamine and tyramine are mixed-acting sympathomimetic amines in the brain | journal = Life Sci | volume = 58 | issue = 23 | pages = 2101–2114 | date = 1996 | pmid = 8649195 | doi = 10.1016/0024-3205(96)00204-4 | url = }}</ref> That is, it enhances the [[action potential]]-mediated release of these [[monoamine neurotransmitter]]s.<ref name="ShimazuMiklya2004" /><ref name="Knoll2003" /><ref name="KnollMiklyaKnoll1996" /> The compound is active as a MAE at much lower concentrations than the concentrations at which it induces the release of catecholamines.<ref name="ShimazuMiklya2004" /><ref name="Knoll2003" /><ref name="KnollMiklyaKnoll1996" /> The MAE actions of phenethylamine and other MAEs may be mediated by TAAR1 agonism.<ref name="HarsingKnollMiklya2022">{{cite journal | vauthors = Harsing LG, Knoll J, Miklya I | title = Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum | journal = Int J Mol Sci | volume = 23 | issue = 15 | date = August 2022 | page = 8543 | pmid = 35955676 | pmc = 9369307 | doi = 10.3390/ijms23158543 | doi-access = free | url = }}</ref><ref name="HarsingTimarMiklya2023">{{cite journal | vauthors = Harsing LG, Timar J, Miklya I | title = Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline | journal = Int J Mol Sci | volume = 24 | issue = 17 | date = August 2023 | page = 13334 | pmid = 37686140 | pmc = 10487936 | doi = 10.3390/ijms241713334 | doi-access = free | url = }}</ref> [[Synthetic compound|Synthetic]] and more [[potency (pharmacology)|potent]] MAEs like [[phenylpropylaminopentane]] (PPAP) and [[selegiline]] (<small>L</small>-deprenyl) have been [[chemical derivative|derived]] from phenethylamine.<ref name="ShimazuMiklya2004" /><ref name="Knoll2003" /><!--

Possibly add something here from this ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205048/

--><!--

INCOMPLETE TABLE:

{| class="wikitable unsortable" style="text-align:center; float:left"

|+ Human [[G protein-coupled receptor|GPCR]] and [[enzyme]] binding data (''incomplete'')

! GPCR target !! [[EC50|EC₅₀]] ({{abbr|nM|nanomolar}}) !! Entry note !! <small>Sources</small>

|-

| [[hTAAR1]] || 300 || Full agonist || <ref name="Human trace amines and hTAARs October 2016 review"/>

|-

! Inhibited enzyme !! [[IC50|IC₅₀]] ({{abbr|nM|nanomolar}}) !! Entry note !! <small>Sources</small>

|-

| [[CYP2A6]] || 4,410 || || <ref name="BindingDB">{{cite web |title=BDBM10758 (2-phenylethan-1-amine &#124; phenylethylamine) |url=http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=10758 |website=BindingDB |publisher=The Binding Database |access-date=30 January 2017}}</ref>

|-

|}-->

{{clear right}}

{{Catecholamine and trace amine biosynthesis|align=right}}

By [[oral route]], phenethylamine's [[half-life]] is {{nowrap|5–10}}&nbsp;minutes;<ref name="Pubchem exogenous half-life">{{cite web |title=Phenethylamine: Pharmacology and Biochemistry |url=https://pubchem.ncbi.nlm.nih.gov/compound/1001?from=summary#section=Pharmacology-and-Biochemistry |work=PubChem |publisher= United States National Library of Medicine&nbsp;– National Center for Biotechnology Information |quote= Plasma Pharmacokinetics of PEA Could Be Described By 1st-Order Kinetics With Estimated T/2 of Approx 5-10 Min.}}</ref> endogenously produced PEA in catecholamine neurons has a half-life of roughly 30&nbsp;seconds.<ref name="Renaissance"/> In humans, PEA is metabolized by [[Phenylethanolamine N-methyltransferase|phenylethanolamine ''N''-methyltransferase]] (PNMT),<ref name="Renaissance"/><ref name="Vascular"/><ref name="HMDB PEA"/><ref name="pmid7432557">{{cite journal | vauthors = Pendleton RG, Gessner G, Sawyer J | title = Studies on lung N-methyltransferases, a pharmacological approach | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 313 | issue = 3 | pages = 263–268 | date = September 1980 | pmid = 7432557 | doi = 10.1007/BF00505743 | s2cid = 1015819 }}</ref> [[MAO-A|monoamine oxidase A]] ({{nowrap|MAO-A}}),<ref name="HMDB PEA"/><ref name="PEA_MAO-A_and_B_Substrate-Suzuki"/> [[MAO-B|monoamine oxidase B]] ({{nowrap|MAO-B}}),<ref name="Renaissance"/><ref name="Vascular"/><ref name="HMDB PEA"/><ref name="PEA_MAO-B_Substrate-Yang"/> the [[semicarbazide-sensitive amine oxidase]]s (SSAOs) [[AOC2]] and [[AOC3]],<ref name="HMDB PEA"/><ref name="SSAO">{{cite journal | vauthors = Kaitaniemi S, Elovaara H, Grön K, Kidron H, Liukkonen J, Salminen T, Salmi M, Jalkanen S, Elima K | title = The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase | journal = Cellular and Molecular Life Sciences | volume = 66 | issue = 16 | pages = 2743–2757 | date = August 2009 | pmid = 19588076 | doi = 10.1007/s00018-009-0076-5 | quote = 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. | s2cid = 30090890 | pmc = 11115939 }}</ref> [[flavin-containing monooxygenase 3]] (FMO3),<ref name="FMO">{{cite journal | vauthors = Krueger SK, Williams DE | title = Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism | journal = Pharmacology & Therapeutics | volume = 106 | issue = 3 | pages = 357–387 | date = June 2005 | pmid = 15922018 | pmc = 1828602 | doi = 10.1016/j.pharmthera.2005.01.001 | quote = 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)&nbsp;... 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, 1997b). }}</ref><ref name="FMO3 catecholamines">{{cite journal | vauthors = Robinson-Cohen C, Newitt R, Shen DD, Rettie AE, Kestenbaum BR, Himmelfarb J, Yeung CK | title = Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease Progression, and Mortality in CKD Patients | journal = PLOS ONE | volume = 11 | issue = 8 | pages = e0161074 | date = August 2016 | pmid = 27513517 | pmc = 4981377 | doi = 10.1371/journal.pone.0161074 | quote = TMAO is generated from trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase isoform 3 (FMO3).&nbsp;... FMO3 catalyzes the oxidation of catecholamine or catecholamine-releasing vasopressors, including tyramine, phenylethylamine, adrenaline, and noradrenaline [32, 33]. | doi-access = free | bibcode = 2016PLoSO..1161074R }}</ref> and [[aralkylamine N-acetyltransferase]] (AANAT).<ref name="HMDB PEA"/><ref>{{cite web|title=EC 2.3.1.87 – Aralkylamine N-acetyltransferase|url=http://www.brenda-enzymes.org/enzyme.php?ecno=2.3.1.87&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0|website=BRENDA|publisher=Technische Universität Braunschweig|access-date=10 November 2014|date=July 2014}}</ref> {{nowrap|[[N-methylphenethylamine|''N''-Methylphenethylamine]]}}, an [[isomer]] of [[amphetamine]], is produced in humans via the metabolism of phenethylamine by PNMT.<ref name="Renaissance"/><ref name="Vascular"/><ref name="pmid7432557"/> [[β-Phenylacetic acid]] is the primary urinary metabolite of phenethylamine and is produced via [[monoamine oxidase]] metabolism and subsequent [[aldehyde dehydrogenase]] metabolism.<ref name="HMDB PEA"/> [[Phenylacetaldehyde]] is the intermediate product which is produced by monoamine oxidase and then further metabolized into β-phenylacetic acid by aldehyde dehydrogenase.<ref name="HMDB PEA"/><ref>{{cite web|title=Aldehyde dehydrogenase – Homo sapiens|url=http://www.brenda-enzymes.org/enzyme.php?ecno=1.2.1.3&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0|website=BRENDA|publisher=Technische Universität Braunschweig|access-date=13 April 2015|date=January 2015}}</ref>

When the initial phenylethylamine concentration in the brain is low, brain levels can be increased {{nowrap|1000-fold}} when taking a [[monoamine oxidase inhibitor]] (MAOI), particularly a [[Monoamine oxidase inhibitor#List of MAO inhibiting drugs|MAO-B inhibitor]], and by {{nowrap|3–4}}&nbsp;times when the initial concentration is high.<ref name=Sabelli78>{{cite journal | vauthors = Sabelli HC, Borison RL, Diamond BI, Havdala HS, Narasimhachari N | title = Phenylethylamine and brain function | journal = Biochemical Pharmacology | volume = 27 | issue = 13 | pages = 1707–1711 | year = 1978 | pmid = 361043 | doi = 10.1016/0006-2952(78)90543-9 }}</ref>

{{clear}}

== See also ==

*[[Alexander Shulgin]]

*[[N-Methylphenethylamine|''N''-Methylphenethylamine]]

*[[PiHKAL]]

==Notes==

{{Reflist|group=note}}

== References ==

{{Reflist|30em}}

== External links ==

*[http://gmd.mpimp-golm.mpg.de/Spectrums/af2a22f3-4aa9-4e5c-9e61-bf278b87a7c4.aspx Phenethylamine MS Spectrum]

{{Chocolate}}

{{Monoamine releasing agents}}

{{Monoaminergic activity enhancers}}

{{TAAR ligands|state=expanded}}

[[Category:Phenethylamines| ]]

[[Category:Biomolecules]]

[[Category:Euphoriants]]

[[Category:Monoaminergic activity enhancers]]

[[Category:Norepinephrine-dopamine releasing agents]]

[[Category:Phenethylamine alkaloids]]

[[Category:Stimulants]]

[[Category:TAAR1 agonists]]

[[Category:VMAT inhibitors]]