Phenethylamine (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. Phenylethylamine functions as a [1 ] neuromodulator or neurotransmitter in the mammalian central nervous system. It is [2 ] 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 experiences extensive first-pass metabolism by monoamine oxidase B (MAO-B), which turns it into phenylacetic acid. This prevents significant concentrations from reaching the brain in low doses. [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.
Occurrence [ edit ]
Phenethylamine is widely distributed throughout the plant kingdom.
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, pK b = 4.17 (or pK a = 9.83), as measured using the HCl salt, and forms a stable crystalline [6 ] hydrochloride salt with a melting point of 217°C. Phenethylamine is also a skin irritant and possible sensitizer [. Its density is 0.962 g/ml. ] citation needed
Synthesis [ edit ]
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. [7 ]
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. [8 ]
Pharmacology [ edit ]
Phenethylamine, similar to amphetamine in its action,
releases norepinephrine and dopamine. [9 ] [10 ] When taken orally, though, it is rapidly metabolized. [11 ] [12 ]
Abnormally low concentrations of endogenous phenethylamine are found in those suffering from
attention-deficit hyperactivity disorder (ADHD), whereas abnormally high concentrations have been discovered to have a strong, positive correlation with the incidence of [13 ] schizophrenia. [14 ]
Recreational use and addiction [ edit ]
Due in large part to the spread of pharmacological and chemical knowledge among drug users online, phenethylamine has been used recreationally by some. While a few users report using the drug singularly, it is common to combine the drug with
selegiline at low doses. At doses below 10 mg per day, selegiline is MAO-B selective, blocking the metabolism of phenethylamine and allowing the drug to reach the brain and have a psychoactive effect. Users describe the activity profile as being very similar to amphetamine or methamphetamine, but 'cleaner' and intensely euphoric, but having a very short duration, between thirty and sixty minutes. Many of the users have reported addiction, one who reported dosing compulsively, as many as thirty times per day. [15 ] Negative side effects, such as a terrible 'crash,' (a period of heavy depression and lethargy as the drug wears off) and hypertensive crisis due to overdose have been noted. Users who have tried this combination with a non-selective monoamine oxidase inhibitor have reported worse side effects, likely because they are also blocking MAO-A which is needed to metabolize the norepinephrine phenethylamine also releases; Like amphetamine, phenethylamine is a stronger releaser of NE than DA, but under the conditions of this combination, the metabolism of dopamine is blocked while norepinephrine is not, likely explaining the 'clean' feeling and intense euphoria. [16 ]
Pharmacokinetics [ edit ]
Phenylethylamine's half-life is 5 to 10 minutes.
It is metabolized by [17 ] phenylethanolamine N-methyltransferase, [18 ] MAOA, [4 ] MAOB, [3 ] aldehyde dehydrogenase, and dopamine-beta-hydroxylase. [17 ] N-methylphenethylamine, an isomer of amphetamine, is produced when phenethylamine is used as a substrate by phenylethanolamine N-methyltransferase. [18 ] 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. [19 ] [20 ]
Toxicity [ edit ]
Acute toxicity studies on phenethylamine show an LD
50 = 100 mg/kg, after intravenous administration to mice. [21 ]
See also [ edit ]
References [ edit ]
^ Glen R. Hanson, Peter J. Venturelli, Annette E. Fleckenstein (2005-11-03). . Jones and Bartlett Publishers. Drugs and society (Ninth Edition) ISBN 978-0-7637-3732-0 . Retrieved 2011-04-19.
^ 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.
^ 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.
^ 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.
^ T. A. Smith (1977). "Phenethylamine and related compounds in plants." Phytochem. 16 9 – 18.
^ E. B. Leffler, H. M. Spencer and A. Burger (1951) J. Am. Chem. Soc. 73 2611-2613.
^ J. C. Robinson and H. R. Snyder (1955). Organic Syntheses, Coll. Vol. 3, p. 720. http://www.orgsyn.org/orgsyn/pdfs/CV3P0720.pdf
^ 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.
^ 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.
^ EM Parker and LX Cubeddu (April 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.
^ 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.
^ Shulgin, Alexander; Ann Shulgin. "Erowid Online Books : "PIHKAL" - #142 PEA" . Retrieved 2010-05-13.
^ 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.
^ 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.
^ j., Bergman; Yasar, Yasar; Winger, Winger (2001). "Psychomotor stimulant effects of β-phenylethylamine in monkeys treated with MAO-B inhibitors". Psychopharmacology 159 (1): 21–30. doi: 10.1007/s002130100890. PMID 11797065.
^ 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.
^ a b Pendleton RG, Gessner G, Sawyer J (September 1980). "Studies on lung N-methyltransferases, a pharmacological approach". Naunyn Schmiedebergs Arch. Pharmacol. 313 (3): 263–8. doi: 10.1007/BF00505743. PMID 7432557.
^ Broadley, KJ (2010 Mar). "The vascular effects of trace amines and amphetamines". Pharmacology & therapeutics 125 (3): 363–75. doi: 10.1016/j.pharmthera.2009.11.005. PMID 19948186.
^ 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.
^ A. M. Lands and J. I. Grant (1952). "The vasopressor action and toxicity of cyclohexylethylamine derivatives." J. Pharmacol. Exp. Ther. 106 341-345.
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