View source for Phenethylamine

{{distinguish|1-phenylethylamine}}
{{Drugbox | Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 464200154
| IUPAC_name = 2-phenyl-2-ethanamine
| image = Fenyloetyloamina.svg
| image2 = Phenethylamine-3D-balls.png

<!--Clinical data-->
| legal_status = Uncontrolled
| routes_of_administration = Oral

<!--Pharmacokinetic data-->
| metabolism = [[Monoamine oxidase A|MAO-A]], [[Monoamine oxidase B|MAO-B]], [[Phenylethanolamine N-methyltransferase|PNMT]], [[Aldehyde dehydrogenase|ALDH]], [[Dopamine-beta-hydroxylase|DBH]], [[Cytochrome P450 2D6|CYP2D6]]
| elimination_half-life = ~5-10 minutes

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 64-04-0
| PubChem = 1001
| IUPHAR_ligand = 2144
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| 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

<!--Chemical data-->
| C=8 | H=11 | N=1
| molecular_weight = 121.18 g/mol
| smiles = c1ccc(cc1)CCN
| InChI = 1/C8H11N/c9-7-6-8-4-2-1-3-5-8/h1-5H,6-7,9H2
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C8H11N/´´´´´´´´g5-8/h1-5H,6-7,9H2
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = BHHGXPLMPWCGHP-UHFFFAOYSA-N
| synonyms = 2-phenylethylamine, β-phenylethylamine, 1-amino-2-phenylethane

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

'''Phenethylamine''' {{IPAc-en|f|ɛ|n|'|ɛ|θ|ə|l|ɒ|'|m|i:|n}} (PEA), '''β-phenethylamine''', or '''phenylethylamine''' is an organic compound and a [[natural product|natural]] [[monoamine]] [[alkaloid]], a [[trace amine]], and also the [[Substituted phenethylamines|name of a class of chemicals]] with many members well known for [[psychoactive drug]] and [[stimulant]] effects.<ref name="PEA 1">{{cite book
|url=http://books.google.com/books?id=CYVnE2grkusC&pg=PA368
|title=Drugs and society (Ninth Edition)
|isbn=978-0-7637-3732-0
|publisher=Jones and Bartlett Publishers
|author=Glen R. Hanson, Peter J. Venturelli, Annette E. Fleckenstein
|date=2005-11-03
|accessdate=2011-04-19
}}</ref> Phenylethylamine functions as a [[neuromodulator]] or [[neurotransmitter]] in the [[mammalian]] [[central nervous system]].<ref name="PEA 2">{{cite journal |pmid=9160 |year=1976 |last1=Sabelli |first1=HC |last2=Mosnaim |first2=AD |last3=Vazquez |first3=AJ |last4=Giardina |first4=WJ |last5=Borison |first5=RL |last6=Pedemonte |first6=WA |title=Biochemical plasticity of synaptic transmission: A critical review of Dale's Principle |volume=11 |issue=4 |pages=481–524 |journal=Biological psychiatry}}</ref> It is [[biosynthesized]] from the [[amino acid]] [[phenylalanine]] by [[enzymatic]] [[decarboxylation]]. 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]]. It is sold as a [[dietary supplement]] for purported [[Mood (psychology)|mood]] and [[weight loss]]-related [[therapeutic benefit]]s; however, [[oral administration|orally]] ingested phenethylamine experiences extensive [[first-pass metabolism]] by [[monoamine oxidase B]] (MAO-B), which turns it into [[phenylacetic acid]]. This prevents significant [[concentration]]s from reaching the [[brain]] in low doses.<ref name="PEA_MAO-B_Substrate-Yang">{{cite journal |pmid=4748552 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=4748552 |year=1973 |last1=Yang |first1=HY |last2=Neff |first2=NH |title=Beta-phenylethylamine: A specific substrate for type B monoamine oxidase of brain |volume=187 |issue=2 |pages=365–71 |journal=The Journal of pharmacology and experimental therapeutics}}</ref><ref name="PEA_MAO-A_and_B_Substrate-Suzuki">{{cite journal |doi=10.1111/j.1471-4159.1981.tb01734.x |title=Oxidation of ?-Phenylethylamine by Both Types of Monoamine Oxidase: Examination of Enzymes in Brain and Liver Mitochondria of Eight Species |year=1981 |last1=Suzuki |first1=O. |last2=Katsumata |first2=Y. |last3=Oya |first3=M. |journal=Journal of Neurochemistry |volume=36 |issue=3 |pages=1298–301 |pmid=7205271}}</ref>

The group of phenethylamine [[Derivative (chemistry)|derivatives]] is referred to as the phenethylamines. [[Substituted phenethylamine]]s, [[substituted amphetamine]]s, and [[substituted methylenedioxyphenethylamine]]s (MDxx) are a series of broad and diverse classes of compounds derived from phenethylamine that include [[stimulant]]s, [[psychedelic drug|psychedelics]], and [[entactogen]]s, as well as [[anorectic]]s, [[bronchodilator]]s, [[decongestant]]s, and [[antidepressant]]s, among others.

==Occurrence==
Phenethylamine is widely distributed throughout the plant kingdom.<ref>{{cite journal |doi=10.1016/0031-9422(77)83004-5 |title=Phenethylamine and related compounds in plants |year=1977 |last1=Smith |first1=Terence A. |journal=Phytochemistry |volume=16 |issue=1 |pages=9–18}}</ref>

==Chemistry==
Phenethylamine is a primary amine, the amino-group being attached to a [[benzene ring]] through a two-carbon, or [[ethyl group]]. It is a colorless liquid at room temperature. Phenethylamine is soluble in water, [[ethanol]], and [[diethyl ether|ether]]. Similar to other low-molecular-weight amines, it has a fishy odor. Upon exposure to air, it forms a solid [[carbonate]] [[salt]] with [[carbon dioxide]]. Phenethylamine is strongly [[base (chemistry)|basic]], pK<sub>b</sub> = 4.17 (or pK<sub>a</sub> = 9.83), as measured using the HCl salt,<ref>{{cite journal |doi=10.1021/ja01150a055 |title=Dissociation Constants of Adrenergic Amines |year=1951 |last1=Leffler |first1=Esther B. |last2=Spencer |first2=Hugh M. |last3=Burger |first3=Alfred |journal=Journal of the American Chemical Society |volume=73 |issue=6 |pages=2611–3}}</ref> and forms a stable crystalline [[hydrochloride]] salt with a melting point of 217°C. Phenethylamine is also a skin irritant and possible sensitizer.{{citation needed|date=October 2012}} Its density is 0.962 g/ml.

===Synthesis===
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. <!-- 2000 psi. (why in the world wouldya mix SI and imperial units? ) --> Alternative syntheses are outlined in the footnotes to this preparation.<ref>{{cite journal |first1=J. C. |last1=Robinson |first2=H. R. |last2=Snyder |year=1955 |title=β-Phenylethylamine |url=http://www.orgsyn.org/Content/pdfs/procedures/CV3P0720.pdf |journal=Organic Syntheses, Coll |volume=3 |pages=720}}</ref>

A much more convenient method for the synthesis of β-phenethylamine is the reduction of [[Beta-Nitrostyrene|ω-nitrostyrene]] by [[lithium aluminum hydride]] in ether, whose successful execution was first reported by R. F. Nystrom and W. G. Brown in 1948.<ref>{{cite journal |doi=10.1021/ja01191a057 |title=Reduction of Organic Compounds by Lithium Aluminum Hydride. III. Halides, Quinones, Miscellaneous Nitrogen Compounds1 |year=1948 |last1=Nystrom |first1=Robert F. |last2=Brown |first2=Weldon G. |journal=Journal of the American Chemical Society |volume=70 |issue=11 |pages=3738–40 |pmid=18102934}}</ref>

==Pharmacology==
Phenethylamine, similar to amphetamine in its action, [[releasing agent|releases]] [[norepinephrine]] and [[dopamine]].<ref>{{cite journal |doi=10.1016/S0014-2999(98)00191-5 |title=Characterization of β-phenylethylamine-induced monoamine release in rat nucleus accumbens: A microdialysis study |year=1998 |last1=Nakamura |first1=Masato |last2=Ishii |first2=Akira |last3=Nakahara |first3=Daiichiro |journal=European Journal of Pharmacology |volume=349 |issue=2–3 |pages=163–9 |pmid=9671094}}</ref><ref>{{cite journal |author=EM Parker and LX Cubeddu |title=Comparative effects of amphetamine, phenylethylamine and related drugs on dopamine efflux, dopamine uptake and mazindol binding |url=http://jpet.aspetjournals.org/cgi/content/abstract/245/1/199 |pmid=3129549 |journal=Journal of Pharmacology and Experimental Therapeutics |date=April 1988 |volume=245 |issue=1 |pages=199–210 |issn=0022-3565}}</ref><ref>{{cite journal |doi=10.1007/BF00975055 |title=The potentiation of cortical neuron responses to noradrenaline by 2-phenylethylamine is independent of endogenous noradrenaline |year=1993 |last1=Paterson |first1=I. A. |journal=Neurochemical Research |volume=18 |issue=12 |pages=1329–36 |pmid=8272197}}</ref> When taken orally, though, it is rapidly metabolized.<ref>{{cite web | url = http://www.erowid.org/library/books_online/pihkal/pihkal142.shtml | title = Erowid Online Books : "PIHKAL" - #142 PEA | accessdate = 2010-05-13 | last = Shulgin | first = Alexander | author2 = Ann Shulgin}}</ref>

Abnormally low concentrations of endogenous phenethylamine are found in those suffering from [[attention-deficit hyperactivity disorder]] (ADHD),<ref>{{cite journal |doi=10.1016/0006-3223(91)90207-3 |title=Phenylethylaminergic mechanisms in attention-deficit disorder |year=1991 |last1=Baker |first1=G.B. |last2=Bornstein |first2=R.A. |last3=Rouget |first3=A.C. |last4=Ashton |first4=S.E. |last5=Van Muyden |first5=J.C. |last6=Coutts |first6=R.T. |journal=Biological Psychiatry |volume=29 |pages=15–22 |pmid=2001444 |issue=1}}</ref> whereas abnormally high concentrations have been discovered to have a strong, positive correlation with the incidence of [[schizophrenia]].<ref>{{cite journal |doi=10.1126/science.504988 |title=Phenylethylamine in paranoid chronic schizophrenia |year=1979 |last1=Potkin |first1=S. |last2=Karoum |first2=F |last3=Chuang |first3=L. |last4=Cannon-Spoor |first4=H. |last5=Phillips |first5=I |last6=Wyatt |first6=R. |journal=Science |volume=206 |issue=4417 |pages=470–1 |pmid=504988}}</ref>

==Pharmacokinetics==
Phenylethylamine's half-life is 5 to 10 minutes.<ref name=SabelliJavaid95 /> It is metabolized by [[phenylethanolamine N-methyltransferase]],<ref name="pmid7432557">{{cite journal |doi=10.1007/BF00505743 |title=Studies on lung N-methyltransferases, a pharmacological approach |year=1980 |last1=Pendleton |first1=Robert G. |last2=Gessner |first2=George |last3=Sawyer |first3=John |journal=Naunyn-Schmiedeberg's Archives of Pharmacology |volume=313 |issue=3 |pages=263–8 |pmid=7432557}}</ref> [[MAO-A|MAOA]],<ref name="PEA_MAO-A_and_B_Substrate-Suzuki" /> [[MAO-B|MAOB]],<ref name="PEA_MAO-B_Substrate-Yang" /> [[aldehyde dehydrogenase]], and [[dopamine-beta-hydroxylase]].<ref name=SabelliJavaid95>{{cite journal | title = Phenylethylamine modulation of affect: therapeutic and diagnostic implications | last = Sabelli | first = Hector C. | author2 = J. I. Javaid | journal = J Neuropsychiatry Clin Neurosci | date = February 1, 1995 | volume = 7 | pages = 6–14 | pmid = 7711493 | url = http://neuro.psychiatryonline.org/cgi/content/abstract/7/1/6 | issue = 1 | issn = 0895-0172}}</ref>  [[N-methylphenethylamine]], an [[isomer]] of [[amphetamine]], is produced when phenethylamine is used as a substrate by [[phenylethanolamine N-methyltransferase]].<ref name="pmid7432557" /><ref>{{cite journal |doi=10.1016/j.pharmthera.2009.11.005 |title=The vascular effects of trace amines and amphetamines |year=2010 |last1=Broadley |first1=Kenneth J. |journal=Pharmacology & Therapeutics |volume=125 |issue=3 |pages=363–75 |pmid=19948186}}</ref>
When the initial phenylethylamine brain concentration is low, brain levels can be increased 1000-fold when taking an MAO inhibitor (MAOI), and by 3-4 times when the initial concentration is high.<ref name=Sabelli78>{{cite journal |doi=10.1016/0006-2952(78)90543-9 |title=Phenylethylamine and brain function |year=1978 |last1=Sabelli |first1=Hector C. |last2=Borison |first2=Richard L. |last3=Diamond |first3=Bruce I. |last4=Havdala |first4=Henri S. |last5=Narasimhachari |first5=Nedathur |journal=Biochemical Pharmacology |volume=27 |issue=13 |pages=1707–11 |pmid=361043}}</ref>

==Toxicity==
Acute toxicity studies on phenethylamine show an LD<sub>50</sub> = 100&nbsp;mg/kg, after intravenous administration to mice; substantial liver damage.<ref>{{cite journal |pmid=13000630 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=13000630 |year=1952 |last1=Lands |first1=AM |last2=Grant |first2=JI |title=The vasopressor action and toxicity of cyclohexylethylamine derivatives |volume=106 |issue=3 |pages=341–5 |journal=The Journal of pharmacology and experimental therapeutics}}</ref>

<!--==Chocolate theory of love==
In the early 1980s, psychiatrist [[Michael Liebowitz]], author of the popular 1983 book ''The Chemistry of Love'', remarked to reporters, "[[chocolate]] is loaded with PEA [ or Phenethylamine ]". This became the focus for an article in ''The New York Times'', which was then taken up by the wire services and then by magazine free-lancers, evolving into the now-eponymous "chocolate theory of love".<ref>Liebowitz, Michael, R. (1983). ''The Chemistry of Love''. Boston: Little, Brown, & Co.{{pn}}</ref> However, as noted earlier, phenethylamine is rapidly metabolized by the enzyme [[MAO-B|MAOB]], preventing significant concentrations from reaching the brain, thus contributing no perceptible psychoactive effect without the use of an MAOI.

Censoring author's comment: this seems like an unscientific fringe theory regarding this substance.  I'd appreciate it if someone more familiar with wp:fringe could take a look at this and decide whether or not to keep the section.-->

==See also==
* [[Trace amine]]s
* [[N-Methylphenethylamine|''N''-Methylphenethylamine]]
* [[Amphetamine]]
* [[Alexander Shulgin]]
* [[PiHKAL]]
* [[Substituted phenethylamine]]

==References==
{{Reflist|2}}

==External links==
* [http://www.erowid.org/library/books_online/pihkal/pihkal.shtml Book II of PiHKAL] online
* [http://pihkal.info/read.php?domain=pk&id=142 Phenethylamine entry in PiHKAL • info]
* Review and summary of PiHKAL, including table of 300+ phenethylamines: [http://www.erowid.org/archive/hyperreal/drugs/psychedelics/phenethylamines/pihkal.review ascii] [http://www.erowid.org/archive/hyperreal/drugs/psychedelics/phenethylamines/pihkal.review.ps postscript]
* [http://www.erowid.org/archive/rhodium/chemistry/pihkaltour/ A Structural Tour of PiHKAL]

{{Adrenergics}}
{{Amphetamine}}
{{Dopaminergics}}
{{Neurotransmitters}}
{{Phenethylamines}}
{{PiHKAL}}
{{Serotonergics}}
{{TAAR ligands}}

[[Category:Phenethylamines| ]]
[[Category:TAAR1 agonists]]
[[Category:Amphetamine]]