Phenethylamine

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Not to be confused with 1-phenylethylamine.
Phenethylamine
Systematic (IUPAC) name
phenylethan-2-amine
Clinical data
Pregnancy cat.  ?
Legal status Uncontrolled
Routes Oral
Pharmacokinetic data
Metabolism MAO-A, MAO-B, ALDH, DBH, CYP2D6
Half-life ~5-10 minutes
Identifiers
CAS number 64-04-0 YesY
ATC code  ?
PubChem CID 1001
IUPHAR ligand 2144
ChemSpider 13856352 YesY
UNII 327C7L2BXQ YesY
ChEBI CHEBI:18397 YesY
ChEMBL CHEMBL610 YesY
NIAID ChemDB 018561
Synonyms 2-phenylethylamine, β-phenylethylamine, 1-amino-2-phenylethane
Chemical data
Formula C8H11N 
Mol. mass 121.18 g/mol
Physical data
Boiling point 195 °C (383 °F)
 N (what is this?)  (verify)

Phenethylamine /fɛnˈɛθəlɒˈmiːn/ (PEA), β-phenethylamine, or phenylethylamine is an organic compound and a natural monoamine alkaloid, a trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects.[1] Phenylethylamine functions as a neuromodulator or neurotransmitter in the mammalian central nervous system.[2] 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 microbial fermentation. It is sold as a dietary supplement for purported mood and weight loss-related therapeutic benefits; however, orally ingested phenethylamine is usually inactive because of extensive first-pass metabolism by monoamine oxidase (MAO) into phenylacetic acid. This prevents significant concentrations from reaching the brain.[3][4]

The group of phenethylamine derivatives is referred to as the phenethylamines. Substituted phenethylamines, substituted amphetamines, and substituted methylenedioxyphenethylamines (MDxx) are a series of broad and diverse classes of compounds derived from phenethylamine that include stimulants, psychedelics, and entactogens, as well as anorectics, bronchodilators, decongestants, and antidepressants, among others.

Contents

Occurrence[edit]

Phenethylamine is widely distributed throughout the plant kingdom.[5]

Chemistry[edit]

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 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, pKb = 4.17 (or pKa = 9.83), as measured using the HCl salt,[6] 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]. Its density is 0.962 g/ml.

Synthesis[edit]

An older method for preparing β-phenethylamine is given in Organic Syntheses, and 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.[7]

A much more convenient method for the synthesis of β-phenethylamine is the reduction of ω-nitrostyrene by lithium aluminum hydride in ether, which was first reported by Nystrom and Brown in 1948.[8]

Pharmacology[edit]

Phenethylamine, similar to amphetamine in its action, releases norepinephrine and dopamine.[9][10][11] When taken orally, though, it is rapidly metabolized.[12]

Abnormally low concentrations of endogenous phenethylamine are found in those suffering from attention-deficit hyperactivity disorder (ADHD),[13] whereas abnormally high concentrations have been discovered to have a strong, positive correlation with the incidence of schizophrenia.[14]

Pharmacokinetics[edit]

Phenylethylamine's half-life is 5 to 10 minutes.[15] It is metabolized by MAOA,[4] MAOB,[3] aldehyde dehydrogenase, and dopamine-beta-hydroxylase.[15] 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.[16]

Toxicity[edit]

Acute toxicity studies on phenethylamine show an LD50 = 100 mg/kg, after intravenous administration to mice.[17]

Chocolate theory of love[edit]

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".[18] However, as noted earlier, phenethylamine is rapidly metabolized by the enzyme MAOB, preventing significant concentrations from reaching the brain, thus contributing no perceptible psychoactive effect without the use of an MAOI.

See also[edit]

References[edit]

  1. ^ Glen R. Hanson, Peter J. Venturelli, Annette E. Fleckenstein (2005-11-03). Drugs and society (Ninth Edition). Jones and Bartlett Publishers. ISBN 978-0-7637-3732-0. Retrieved 2011-04-19. 
  2. ^ Sabelli HC, Mosnaim AD, Vazquez AJ, Giardina WJ, Borison RL, Pedemonte WA (1976-08-11). "Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle.". PubMed. Retrieved 2011-04-19. 
  3. ^ a b Yang HY, Neff NH. (November 1973). "Beta-phenylethylamine: a specific substrate for type B monoamine oxidase of brain". The Journal of Pharmacology and Experimental Therapeutics 187 (2): 365–71. ISSN 0022-3565. PMID 4748552. 
  4. ^ a b Suzuki O, Katsumata Y, Oya M. (March 1981). "Oxidation of beta-phenylethylamine by both types of monoamine oxidase: examination of enzymes in brain and liver mitochondria of eight species". The Journal of Neurochemistry 36 (3): 1298–301. doi:10.1111/j.1471-4159.1981.tb01734.x. ISSN 0022-3042. PMID 7205271. 
  5. ^ T. A. Smith (1977). "Phenethylamine and related compounds in plants." Phytochem. 16 9 – 18.
  6. ^ E. B. Leffler, H. M. Spencer and A. Burger (1951) J. Am. Chem. Soc. 73 2611-2613.
  7. ^ J. C. Robinson and H. R. Snyder (1955). Organic Syntheses, Coll. Vol. 3, p. 720. http://www.orgsyn.org/orgsyn/pdfs/CV3P0720.pdf
  8. ^ R. F. Nystrom and W. G. Brown (1948)."Reduction of organic compounds by lithium aluminum hydride. III. Halides, quinones, miscellaneous nitrogen compounds." J. Am. Chem. Soc. 70 3738-3740.
  9. ^ Nakamura, Ishii, Nakahara (1998). "Characterization of β-phenylethylamine-induced monoamine release in rat nucleus accumbens : a microdialysis study". European Journal of Pharmacology 349 (2–3): 163–9. doi:10.1016/S0014-2999(98)00191-5. PMID 9671094. 
  10. ^ EM Parker and LX Cubeddu (04/01/1988). "Comparative effects of amphetamine, phenylethylamine and related drugs on dopamine efflux, dopamine uptake and mazindol binding". Journal of Pharmacology and Experimental Therapeutics 245 (1): 199–210. ISSN 0022-3565. PMID 3129549. 
  11. ^ I. A. Paterson (1993). "The potentiation of cortical neuron responses to noradrenaline by 2-phenylethylamine is independent of endogenous noradrenaline". Neurochemical Research 18 (12): 1329–36. doi:10.1007/BF00975055. PMID 8272197. 
  12. ^ Shulgin, Alexander; Ann Shulgin. "Erowid Online Books : "PIHKAL" - #142 PEA". Retrieved 2010-05-13. 
  13. ^ Baker GB et al. (1991). "Phenylethylaminergic mechanisms in attention-deficit disorder". Biological Psychiatry 29 (1): 15–22. doi:10.1016/0006-3223(91)90207-3. PMID 2001444. 
  14. ^ SG Potkin et al. (October 1979). "Phenylethylamine in paranoid chronic schizophrenia". Science 206 (4417): 470–1. doi:10.1126/science.504988. ISSN 0036-8075. PMID 504988. 
  15. ^ a b Sabelli, Hector C.; J. I. Javaid (February 1, 1995). "Phenylethylamine modulation of affect: therapeutic and diagnostic implications". J Neuropsychiatry Clin Neurosci 7 (1): 6–14. ISSN 0895-0172. PMID 7711493. 
  16. ^ Sabelli, Hector C.; et al. (1978). "Phenylethylamine and brain function". Biochem Pharmacol. 27 (13): 1707–11. doi:10.1016/0006-2952(78)90543-9. ISSN 0006-2952. PMID 361043. 
  17. ^ A. M. Lands and J. I. Grant (1952). "The vasopressor action and toxicity of cyclohexylethylamine derivatives." J. Pharmacol. Exp. Ther. 106 341-345.
  18. ^ Liebowitz, Michael, R. (1983). The Chemistry of Love. Boston: Little, Brown, & Co.

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