Phenethylamine

Chembox new
Name = Phenethylamine
Reference ="Merck Index", 12th Edition, 7371.]
ImageFile = Fenyloetyloamina.svg
ImageName = Chemical structure of Phenethylamine
IUPACName = 2-Phenylethylamine
OtherNames = Phenethylamine
β-Phenylethylamine
2-Phenyl-1-aminoethane
β-Aminoethylamine
2-Phenylethanamine
Section1 = Chembox Identifiers
CASNo = 64-04-0
SMILES = c1ccccc1CCN
Section2 = Chembox Properties
Formula = C₈H₁₁N
MolarMass = 121.18 g/mol
Density = 0.964 g/cm³
MeltingPt = -60 °C
BoilingPt = 194.5-195 °C
Section7 = Chembox Hazards
ExternalMSDS = [http://www.sciencelab.com/xMSDS-Phenethylamine-9927690 MSDS for phenethylamine]
NFPA-H = 2
NFPA-F = 2
NFPA-R = 2

Phenethylamine, or "β"-phenylethylamine or 2-phenylethylamine, is an alkaloid and monoamine. Phenethylamine also has a constitutional isomer "α"-phenylethylamine (1-phenylethylamine), which has two stereoisomers: ("R")-(+)-1-phenylethylamine and ("S")-(-)-1-phenylethylamine. In the human brain, 2-phenethylamine is believed to function as a neuromodulator or neurotransmitter (trace amine). Phenethylamine is a natural compound biosynthesized from the amino acid phenylalanine by enzymatic decarboxylation. It is also found in many foods such as chocolate, especially after microbial fermentation. However trace amounts from food is quickly metabolized by the enzyme MAO-B, preventing significant concentrations from reaching the brain.cite journal
author=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
year=1973
pages=365–71
volume=187
issue=2
pmid=4748552] cite journal
author=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=The Journal of Neurochemistry
year=1981
pages=1298–301
volume=36
issue=3
pmid=7205271
doi=10.1111/j.1471-4159.1981.tb01734.x ]

Phenylethylamine is a precursor to the neurotransmitter phenylethanolamine. [cite journal| journal=Nature |volume=248 |year=1974 |title=2-Phenylethylamine as a possible mediator for THC induced stimulation]

D-Phenylalanine increases the brain content of phenylethylamine .cite journal |journal=Biochemical Pharmacology |volume=27 |pages=1729–1730| title=Phenylethylamine And Brain Function |author=HECTOR C. SABELLI, RICHARD L. BORISON, BRUCE I. DIAMOND, HENRI S. HAVDALA, and NEDATHUR NARASIMHACHARI |doi=10.1016/0006-2952(78)90548-8 |year=1978] Phenylethylamine has been shown at least indirectly to satisfy the four main criteria required to demonstrate that a neuroamine sustains mood and that its deficit can be responsible for depression. Antidepressant drug therapy is an indirect (pharmacological) "replacement" of brain phenylethylamine .

Substituted phenethylamines are a broad and diverse class of compounds that include stimulants, hallucinogens, entactogens, anorectics, bronchodilators, and antidepressants.

Chemistry

Phenethylamine is an aromatic amine, which is a colorless liquid at room temperature. It is soluble in water, ethanol, and 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 basic and forms a stable crystalline hydrochloride salt with a melting point of 217 °C. Phenethylamine is also a skin irritant and possible sensitizer.

Neurochemistry

Infusion of phenylethylamine increased extracellular levels of dopamine [cite journal |author=Nakamura, Ishii, Nakahara
title=Characterization of β-phenylethylamine-induced monoamine release in rat nucleus accumbens : a microdialysis study
journal=European journal of pharmacology|url=http://cat.inist.fr/?aModele=afficheN&cpsidt=2350263] while at the same time inhibiting DA neuron firings. [cite journal |author=Kota Ishida, Mikio Murata et al.
title=Effects of -Phenylethylamine on Dopaminergic Neurons of the Ventral Tegmental Area in the Rat: A Combined Electrophysiological and Microdialysis Study|journal=Journal of Pharmacology and Experimental Therapeutics Fast Forward
url=http://jpet.aspetjournals.org/cgi/content/full/314/2/916
pmid=15879004
doi=10.1124/jpet.105.084764
year=2005
volume=314
pages=916] [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
format=abstract] It also modulates noradrenergic transmission. [cite journal |author=I. A. Paterson|title=The potentiation of cortical neuron responses to noradrenaline by 2-phenylethylamine is independent of endogenous noradrenaline|journal=Neurochemical Resarch|url=http://www.springerlink.com/content/l221368846768g16/|doi=10.1007/BF00975055|year=1993|volume=18|pages=1329] Phenethylamine, along with tyramine, reversibly depresses the slow GABA_B receptor inhibitory post-synaptic potential in midbrain dopaminergic cells. [cite journal |author=M Federici et al.
format = abstract
title = Trace amines depress GABA B response in dopaminergic neurons by inhibiting G-betagamma-gated inwardly rectifying potassium channels
journal = Molecular Pharmacology
volume = 67
pages = 1283–1290
year = 2005
url = http://molpharm.aspetjournals.org/cgi/content/full/67/4/1283
doi = 10.1124/mol.104.007427
pmid = 15644497 ]

Low levels are found in those suffering from attention deficit disorder [cite journal |author=Baker GB et al.|title=Phenylethylaminergic mechanisms in attention-deficit disorder|url=http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2001444&dopt=AbstractPlus] and often in depression, while levels are elevated in schizophrenia. [cite journal |author=SG Potkin et al |title=Phenylethylamine in paranoid chronic schizophrenia |doi= 10.1126/science.504988 |year=1979 |journal=Science |volume=206 |pages=470 |pmid=504988] This is associated with low dopamine in ADHD and depression and high dopamine in schizophrenia.

Chocolate theory of love

In the early 1980s, researcher Michael Liebowitz, author of the popular 1983 book "The Chemistry of Love", remarked to reporters that "chocolate is loaded with PEA." This became the focus for an article in "The New York Times", which was then taken up by the wire services, then by magazine free-lancers, and evolved into the now-eponymous "chocolate theory of love." [Liebowitz, Michael, R. (1983). "The Chemistry of Love". Boston: Little, Brown, & Co.] However, as noted earlier, phenethylamine is rapidly metabolized by the enzyme MAO-B, preventing significant concentrations from reaching the brain, thus contributing no perceptible psychoactive effect in the absence of a ayahuasca-like mixture.

ubstituted phenethylamines

Substituted phenethylamines carry additional chemical modifications at the phenyl ring, the sidechain, or the amino group:

* Substituted Amphetamines are homologues of phenethylamines carrying an alpha-methyl ("α"-CH₃) group at the sidechain carbon atom next to the amino group.
* Catecholamines are phenethylamines carrying two hydroxy groups in positions 3 and 4 of the phenyl ring. Examples are the hormones and neurotransmitters dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline).
* The aromatic amino acids phenylalanine and tyrosine are phenethylamines carrying a carboxyl group (COOH) in alpha position.
* 2Cs are phenethylamines with methoxy groups attached to the 2 and 5 carbons and no alpha-methyl group.

Pharmacology

Phenylethylamine's half life is 5-10 minutes.Dubious|date=May 2008Phenylethylamine is metabolized by MAO-A , MAO-B , aldehyde dehydrogenase and dopamine-beta-hydroxylase.cite journal | title = Phenylethylamine modulation of affect: therapeutic and diagnostic implications | last = Sabelli | first = Hector C. | coauthors = J. I. Javaid | journal = J Neuropsychiatry Clin Neurosci | year = 1995 | volume = 7 | pages = 6–14 | pmid = 7711493 | url = http://neuro.psychiatryonline.org/cgi/content/abstract/7/1/6] Phenylethylamine brain levels can be increased by a 1000 fold when taking an MAO Inhibitor and 3-4 times when taken by itself.cite journal | title = Phenylethylamine and brain function | last = Sabelli | first = Hector C. | coauthors = et al. | journal = Biochem Pharmacol. | year = 1978 | volume = 27 | issue = 13 | pages = 1707–1711 | pmid = 361043 | doi = 10.1016/0006-2952(78)90543-9] Dubious|date=May 2008Alcohol and THC increase phenylethylamine levels by a 4 fold.Dubious|date=May 2008

Many substituted phenethylamines are pharmacologically active drugs due to their similarity to the monoamine neurotransmitters:

* Stimulants like the plant alkaloids ephedrine and cathinone and the synthetic drug dextroamphetamine and methylphenidate
* Hallucinogens like the plant alkaloid mescaline and the synthetic drug 2C-B
* Empathogen-entactogens like MDMA ("ecstasy") and MDA
* Anorectics like phentermine, fenfluramine, and amphetamine
* Bronchodilators like salbutamol and ephedrine
* Antidepressants like venlafaxine, bupropion and the monoamine oxidase inhibitors phenelzine and tranylcypromine.

ubstitution table

Some of the more important phenethylamines are tabulated below. For simplicity, the stereochemistry of the sidechain is not covered in the table. Hundreds of other simple synthetic phenethylamines are known. This is due in large part to the pioneering work of Alexander Shulgin, much of which is described in the book "PiHKAL (Phenethylamines i Have Known And Loved)".

Relation to amphetamine

Despite the negative stigma tagged to amphetamine (alpha-methylphenethylamine) ("speed", "amp", "uppers") and methylamphetamine (N-methyl-alpha-methylphenethylamine) ("speed", "meth", "ice", "crystal") and its recreational compounds, the phenylethylamine comprises not only these so called toxic or dangerous amphetamine or methamphetamine, it makes up many drugs with important uses including medical ones like bronchodilators; used for dilating or "opening" the bronchi and bronchioles, which is benefit to and can save the life of an asthmatic (with salbutamol or albuterol or epinephrin for someone with life-threatening allergic reactions), important neurotransmitters like dopamine, epinephrine (Adrenaline), (which humans depend on for normal functioning and survival), and some medically used stimulants like amphetamine (Adderall, Dexedrine), methylamphetamine (Desoxyn), methylphenidate (Ritalin, Concerta and others); which benefit people with ADHD and ADD (attention and behavioral disorders affecting many children and some adults), narcolepsy (person with insomnia that can fall asleep at anytime during the day), chronic fatigue syndrome(CFS), syndrome that inflicts unexplainable pain, fatigue, interruption of normal sleep, cognitive impairments (confusion, forgetfulness, and a cloudy mental or head feeling), ataxia, nausea and gastrointestinal problems like IBS and other negative symptoms, and can be used for traumatic brain injury (TBS). The majority of phenylethylamines used by many have some or all of the actions of the stigmatized amphetamine and methamphetamine (though sometimes they lack the recreational abuse) and also share great structural similarity to methamphetamine and amphetamine.

Graphical overview

ee also

* Catecholamines
* Alexander Shulgin
** PiHKAL (Phenethylamines i Have Known And Loved)"
* Phenethyl alcohol
* 2C's

References

External links

* [http://www.erowid.org/library/books_online/pihkal/pihkal.shtml Book II of PiHKAL] online
* 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]