Phenethylamine
Phenylethylamine or phenethylamine (PEA) is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects.[1] Studies[2] suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the mammalian central nervous system. It is biosynthesized from the amino acid phenylalanine by enzymatic decarboxylation. Besides 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, preventing 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.
Chemistry
Phenethylamine is an amine, consisting of a benzene ring and an aminoethyl 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 and forms a stable crystalline hydrochloride salt with a melting point of 217 °C. Phenethylamine is also a skin irritant and possible sensitizer.
Phenethylamine has an inactive constitutional isomer 1-phenylethylamine, which itself has two stereoisomers: (R)-(+)-1-phenylethylamine and (S)-(-)-1-phenylethylamine.
Pharmacology
Phenethylamine, similar to amphetamine in its action, releases norepinephrine and dopamine.[5][6][7] However, when taken orally it is rapidly metabolized.[8]
Abnormally low concentrations of endogenous phenethylamine are found in those suffering from attention-deficit hyperactivity disorder (ADHD)[9] and often in clinical depression, whereas abnormally high concentrations have been discovered to have a strong, positive correlation with the incidence of schizophrenia.[10]
Pharmacokinetics
Phenylethylamine's half-life is 5–10 minutes.[11] Phenylethylamine is metabolized by MAO-A,[4] MAO-B,[3] aldehyde dehydrogenase, and dopamine-beta-hydroxylase.[11] When initial phenylethylamine brain concentration are low, phenylethylamine brain levels can be increased by a 1000-fold when taking a MAO Inhibitor, and by 3-4 times when the initial concentration are high. [12] Alcohol and THC increase phenylethylamine levels by a 4-fold.[12]
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 and then by magazine free-lancers, evolving into the now-eponymous "chocolate theory of love."[13] 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 without the use of a monoamine oxidase inhibitor (MAOI).
See also
References
- ^ Glen R. Hanson, Peter J. Venturelli, Annette E. Fleckenstein (2005-11-03). "Drugs and society (Ninth Edition)". Jones and Bartlett Publishers. ISBN 9780763737320. http://books.google.com/books?id=CYVnE2grkusC&pg=PA368. 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. http://www.ncbi.nlm.nih.gov/pubmed/9160/. 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. http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+64-04-0.
- ^ 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. http://cat.inist.fr/?aModele=afficheN&cpsidt=2350263.
- ^ 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. http://jpet.aspetjournals.org/cgi/content/abstract/245/1/199.
- ^ 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. http://www.springerlink.com/content/l221368846768g16/.
- ^ Shulgin, Alexander; Ann Shulgin. "Erowid Online Books : "PIHKAL" - #142 PEA". http://www.erowid.org/library/books_online/pihkal/pihkal142.shtml. 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.
- ^ 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. http://neuro.psychiatryonline.org/cgi/content/abstract/7/1/6.
- ^ a b 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.
- ^ Liebowitz, Michael, R. (1983). The Chemistry of Love. Boston: Little, Brown, & Co.
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See also Sympathomimetic amines
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Agonists: 5-FNE • 6-FNE • Amidephrine • Anisodamine • Anisodine • Cirazoline • Dipivefrine • Dopamine • Ephedrine • Epinephrine (Adrenaline) • Etilefrine • Ethylnorepinephrine • Indanidine • Levonordefrin • Metaraminol • Methoxamine • Methyldopa • Midodrine • Naphazoline • Norepinephrine (Noradrenaline) • Octopamine • Oxymetazoline • Phenylephrine • Phenylpropanolamine • Pseudoephedrine • Synephrine • Tetrahydrozoline
Antagonists: Abanoquil • Adimolol • Ajmalicine • Alfuzosin • Amosulalol • Arotinolol • Atiprosin • Benoxathian • Buflomedil • Bunazosin • Carvedilol • CI-926 • Corynanthine • Dapiprazole • DL-017 • Domesticine • Doxazosin • Eugenodilol • Fenspiride • GYKI-12,743 • GYKI-16,084 • Indoramin • Ketanserin • L-765,314 • Labetalol • Mephendioxan • Metazosin • Monatepil • Moxisylyte (Thymoxamine) • Naftopidil • Nantenine • Neldazosin • Nicergoline • Niguldipine • Pelanserin • Phendioxan • Phenoxybenzamine • Phentolamine • Piperoxan • Prazosin • Quinazosin • Ritanserin • RS-97,078 • SGB-1,534 • Silodosin • SL-89.0591 • Spiperone • Talipexole • Tamsulosin • Terazosin • Tibalosin • Tiodazosin • Tipentosin • Tolazoline • Trimazosin • Upidosin • Urapidil • Zolertine
* Note that many TCAs, TeCAs, antipsychotics, ergolines, and some piperazines like buspirone, trazodone, nefazodone, etoperidone, and mepiprazole all antagonize α1-adrenergic receptors as well, which contributes to their side effects such as orthostatic hypotension.
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CGS-19281A • SKF-64139 • SKF-7698
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Adamantanes: Amantadine • Memantine • Rimantadine; Aminotetralins: 7-OH-DPAT • 8-OH-PBZI • Rotigotine • UH-232; Benzazepines: 6-Br-APB • Fenoldopam • SKF-38,393 • SKF-77,434 • SKF-81,297 • SKF-82,958 • SKF-83,959; Ergolines: Bromocriptine • Cabergoline • Dihydroergocryptine • Lisuride • LSD • Pergolide; Dihydrexidine derivatives: 2-OH-NPA • A-86,929 • Ciladopa • Dihydrexidine • Dinapsoline • Dinoxyline • Doxanthrine; Others: A-68,930 • A-77636 • A-412,997 • ABT-670 • ABT-724 • Aplindore • Apomorphine • Aripiprazole • Bifeprunox • BP-897 • CY-208,243 • Dizocilpine • Etilevodopa • Flibanserin • Ketamine • Melevodopa • Modafinil • Pardoprunox • Phencyclidine • PD-128,907 • PD-168,077 • PF-219,061 • Piribedil • Pramipexole • Propylnorapomorphine • Pukateine • Quinagolide • Quinelorane • Quinpirole • RDS-127 • Ro10-5824 • Ropinirole • Rotigotine • Roxindole • Salvinorin A • SKF-89,145 • Sumanirole • Terguride • Umespirone • WAY-100,635
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Morpholines: Fenbutrazate • Morazone • Phendimetrazine • Phenmetrazine; Oxazolines: 4-Methylaminorex (4-MAR, 4-MAX) • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline • Thozalinone; Phenethylamines (also amphetamines, cathinones, phentermines, etc): 2-Hydroxyphenethylamine (2-OH-PEA) • 4-CAB • 4-Methylamphetamine (4-MA) • 4-Methylmethamphetamine (4-MMA) • Alfetamine • Amfecloral • Amfepentorex • Amfepramone • Amphetamine ( Dextroamphetamine, Levoamphetamine) • Amphetaminil • β-Methylphenethylamine (β-Me-PEA) • Benzodioxolylbutanamine (BDB) • Benzodioxolylhydroxybutanamine (BOH) • Benzphetamine • Buphedrone • Butylone • Cathine • Cathinone • Clobenzorex • Clortermine • D-Deprenyl • Dimethoxyamphetamine (DMA) • Dimethoxymethamphetamine (DMMA) • Dimethylamphetamine • Dimethylcathinone (Dimethylpropion, metamfepramone) • Ethcathinone (Ethylpropion) • Ethylamphetamine • Ethylbenzodioxolylbutanamine (EBDB) • Ethylone • Famprofazone • Fenethylline • Fenproporex • Flephedrone • Fludorex • Furfenorex • Hordenine • Lophophine (Homomyristicylamine) • Mefenorex • Mephedrone • Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine, Levomethamphetamine) • Methcathinone (Methylpropion) • Methedrone • Methoxymethylenedioxyamphetamine (MMDA) • Methoxymethylenedioxymethamphetamine (MMDMA) • Methylbenzodioxolylbutanamine (MBDB) • Methylenedioxyamphetamine (MDA, tenamfetamine) • Methylenedioxyethylamphetamine (MDEA) • Methylenedioxyhydroxyamphetamine (MDOH) • Methylenedioxymethamphetamine (MDMA) • Methylenedioxymethylphenethylamine (MDMPEA, homarylamine) • Methylenedioxyphenethylamine (MDPEA, homopiperonylamine) • Methylone • Ortetamine • Parabromoamphetamine (PBA) • Parachloroamphetamine (PCA) • Parafluoroamphetamine (PFA) • Parafluoromethamphetamine (PFMA) • Parahydroxyamphetamine (PHA) • Paraiodoamphetamine (PIA) • Paredrine (Norpholedrine, Oxamphetamine) • Phenethylamine (PEA) • Pholedrine • Phenpromethamine • Prenylamine • Propylamphetamine • Tiflorex (Flutiorex) • Tyramine (TRA) • Xylopropamine • Zylofuramine; Piperazines: 2,5-Dimethoxy-4-bromobenzylpiperazine (2C-B-BZP) • Benzylpiperazine (BZP) • Methoxyphenylpiperazine (MeOPP, paraperazine) • Methylbenzylpiperazine (MBZP) • Methylenedioxybenzylpiperazine (MDBZP, piperonylpiperazine); Others: 2-Amino-1,2-dihydronaphthalene (2-ADN) • 2-Aminoindane (2-AI) • 2-Aminotetralin (2-AT) • 4-Benzylpiperidine (4-BP) • 5-IAI • Clofenciclan • Cyclopentamine • Cypenamine • Cyprodenate • Feprosidnine • Gilutensin • Heptaminol • Hexacyclonate • Indanylaminopropane (IAP) • Indanorex • Isometheptene • Methylhexanamine • Naphthylaminopropane (NAP) • Octodrine • Phthalimidopropiophenone • Propylhexedrine ( Levopropylhexedrine) • Tuaminoheptane (Tuamine)
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