Global InformationPhenethylamine information
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| Pronunciation | /fɛnˈɛθələmiːn/ |
| Other names | PEA; phenylethylamine, phetamine |
| Dependence liability | Psychological: low–moderate[citation needed] Physical: none |
| Addiction liability | None–Low (w/o an MAO-B inhibitor)[1] Moderate (with an MAO-B inhibitor)[1] |
| Routes of administration | Oral (taken by mouth) |
| Drug class | CNS stimulant, anorectic |
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| Physiological data | |
| Source tissues | Substantia nigra pars compacta; Ventral tegmental area; Locus coeruleus; many others |
| Target tissues | System-wide |
| Receptors | Varies greatly across species; Human receptors: hTAAR1[2] |
| Precursor | L-Phenylalanine[3][4] |
| Biosynthesis | Aromatic L-amino acid decarboxylase (AADC)[3][4] |
| Metabolism | Primarily: MAO-B[3][4][5] Other enzymes: MAO-A,[5][6] SSAOs (AOC2 & AOC3),[5][7] PNMT,[3][4][5] AANAT,[5] FMO3,[8][9] and others |
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| Metabolism | Primarily: MAO-B[3][4][5] Other enzymes: MAO-A,[5][6] SSAOs (AOC2 & AOC3),[5][7] PNMT,[3][4][5] AANAT,[5] FMO3,[8][9] and others |
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| Excretion | Renal (kidneys) |
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| ECHA InfoCard | 100.000.523 |
| Chemical and physical data | |
| Formula | C8H11N |
| Molar mass | 121.183 g·mol−1 |
| 3D model (JSmol) |
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| Density | 0.9640 g/cm3 |
| Melting point | −60 °C (−76 °F) [11] |
| Boiling point | 195 °C (383 °F) [11] |
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Phenethylamine[note 1] (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons.[1][12][13] To a lesser extent, it also acts as a neurotransmitter in the human central nervous system.[14] In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation.[15] In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.
Phenethylamine is sold as a dietary supplement for purported mood and weight loss-related therapeutic benefits; however, in orally ingested phenethylamine, a significant amount is metabolized in the small intestine by monoamine oxidase B (MAO-B) and then aldehyde dehydrogenase (ALDH), which converts it to phenylacetic acid.[5] This means that for significant concentrations to reach the brain, the dosage must be higher than for other methods of administration.[5][6][16] Some authors postulated its role in people's falling-in-love without substantiating it with any direct evidence.[17][18]
Phenethylamines, or more properly, substituted phenethylamines, are the group of phenethylamine derivatives that contain phenethylamine as a "backbone"; in other words, this chemical class includes derivative compounds that are formed by replacing one or more hydrogen atoms in the phenethylamine core structure with substituents. The class of substituted phenethylamines includes all substituted amphetamines, and substituted methylenedioxyphenethylamines (MDxx), and contains many drugs which act as empathogens, stimulants, psychedelics, anorectics, bronchodilators, decongestants, and/or antidepressants, among others.
- ^ a b c Pei Y, Asif-Malik A, Canales JJ (April 2016). "Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications". Frontiers in Neuroscience. 10: 148. doi:10.3389/fnins.2016.00148. PMC 4820462. PMID 27092049.
Furthermore, evidence has accrued on the ability of TAs to modulate brain reward (i.e., the subjective experience of pleasure) and reinforcement (i.e., the strengthening of a conditioned response by a given stimulus; Greenshaw, 2021), suggesting the involvement of the TAs in the neurological adaptations underlying drug addiction, a chronic relapsing syndrome characterized by compulsive drug taking, inability to control drug intake and dysphoria when access to the drug is prevented (Koob, 2009). Consistent with its hypothesized role as "endogenous amphetamine," β-PEA was shown to possess reinforcing properties, a defining feature that underlies the abuse liability of amphetamine and other psychomotor stimulants. β-PEA was also as effective as amphetamine in its ability to produce conditioned place preference (i.e., the process by which an organism learns an association between drug effects and a particular place or context) in rats (Gilbert and Cooper, 1983) and was readily self-administered by dogs that had a stable history (i.e., consisting of early acquisition and later maintenance) of amphetamine or cocaine self-administration (Risner and Jones, 1977; Shannon and Thompson, 1984). In another study, high concentrations of β-PEA dose-dependently maintained responding in monkeys that were previously trained to self-administer cocaine, and pretreatment with a MAO-B inhibitor, which delayed β-PEA deactivation, further increased response rates (Bergman et al., 2001).
- ^ Cite error: The named reference
Human trace amines and hTAARs October 2016 reviewwas invoked but never defined (see the help page). - ^ a b c d e Cite error: The named reference
Renaissancewas invoked but never defined (see the help page). - ^ a b c d Cite error: The named reference
Vascularwas invoked but never defined (see the help page). - ^ a b c d e f g Wishart, David S.; Guo, An Chi; Oler, Eponine; Wang, Fel; Anjum, Afia; Peters, Harrison; Dizon, Raynard; Sayeeda, Zinat; Tian, Siyang; Lee, Brian L.; Berjanskii, Mark; Mah, Robert; Yamamoto, Mai; Jovel Castillo, Juan; Torres Calzada, Claudia; Hiebert Giesbrecht, Mickel; Lui, Vicki W.; Varshavi, Dorna; Varshavi, Dorsa; Allen, Dana; Arndt, David; Khetarpal, Nitya; Sivakumaran, Aadhavya; Harford, Karxena; Sanford, Selena; Yee, Kristen; Cao, Xuan; Budinsky, Zachary; Liigand, Jaanus; Zhang, Lun; Zheng, Jiamin; Mandal, Rupasri; Karu, Naama; Dambrova, Maija; Schiöth, Helgi B.; Gautam, Vasuk. "Showing metabocard for Phenylethylamine (HMDB0012275)". Human Metabolome Database, HMDB. 5.0.
- ^ 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". Journal of Neurochemistry. 36 (3): 1298–1301. doi:10.1111/j.1471-4159.1981.tb01734.x. PMID 7205271. S2CID 36099388.
- ^ Cite error: The named reference
SSAOwas invoked but never defined (see the help page). - ^ Cite error: The named reference
FMOwas invoked but never defined (see the help page). - ^ Cite error: The named reference
FMO3 catecholamineswas invoked but never defined (see the help page). - ^ Cite error: The named reference
Pubchem exogenous half-lifewas invoked but never defined (see the help page). - ^ a b "Chemical and Physical Properties". Phenethylamine. PubChem Compound. United States National Library of Medicine – National Center for Biotechnology Information.
- ^ Cite error: The named reference
PEA VMAT2 MEDRS reviewwas invoked but never defined (see the help page). - ^ Cite error: The named reference
Millerwas invoked but never defined (see the help page). - ^ Sabelli HC, Mosnaim AD, Vazquez AJ, Giardina WJ, Borison RL, Pedemonte WA (August 1976). "Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle". Biological Psychiatry. 11 (4): 481–524. PMID 9160.
- ^ Berry MD (July 2004). "Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators". Journal of Neurochemistry. 90 (2): 257–271. doi:10.1111/j.1471-4159.2004.02501.x. PMID 15228583.
- ^ 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): 365–371. PMID 4748552.
- ^ Godfrey PD, Hatherley LD, Brown RD (1 August 1995). "The Shapes of Neurotransmitters by Millimeter-Wave Spectroscopy: 2-Phenylethylamine". Journal of the American Chemical Society. 117 (31): 8204–8210. doi:10.1021/ja00136a019. ISSN 0002-7863.
- ^ Marazziti D, Canale D (August 2004). "Hormonal changes when falling in love". Psychoneuroendocrinology. 29 (7): 931–936. doi:10.1016/j.psyneuen.2003.08.006. PMID 15177709. S2CID 24651931.
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