Phenethylamine

This article is about 2-phenylethylamine. For its isomer, see 1-phenylethylamine. For its derivatives, see substituted phenethylamine.

Phenethylamine
Clinical data
Pronunciation/fɛnˈɛθələmiːn/
Other namesPhenylethylamine; PEA; β-Phenylethylamine; β-Phenylethylamine; β-PEA; 2-Phenylethylamine; 2-PEA; Phetamine
Dependence
liability		Psychological: low–moderate
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 classNorepinephrine–dopamine releasing agent; Trace amine-associated receptor 1 (TAAR1) agonist; Psychostimulant; Sympathomimetic
ATC code
  • None
Physiological data
Source tissuesSubstantia nigra pars compacta;
Ventral tegmental area;
Locus coeruleus;
many others
Target tissuesSystem-wide
ReceptorsVaries greatly across species;
Human receptors: hTAAR1[2]
PrecursorL-Phenylalanine[3][4]
BiosynthesisAromatic L-amino acid decarboxylase (AADC)[3][4]
MetabolismPrimarily: 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
Legal status
Legal status
  • AU: Unscheduled
  • CA: Unscheduled
  • NZ: Unscheduled
  • UK: Unscheduled
  • US: Unscheduled
  • UN: Unscheduled
Pharmacokinetic data
MetabolismPrimarily: 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
Elimination half-life
  • Exogenous: 5–10 minutes[10]
  • Endogenous: ~30 seconds[3]
ExcretionRenal (kidneys)
Identifiers
IUPAC name
  • 2-Phenylethan-1-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.000.523
Chemical and physical data
FormulaC8H11N
Molar mass121.183 g·mol−1
3D model (JSmol)
Density0.9640 g/cm3 [10]
Melting point−60 °C (−76 °F) [10]
Boiling point195 °C (383 °F) [10]
SMILES
  • NCCc1ccccc1
InChI
  • InChI=1S/C8H11N/c9-7-6-8-4-2-1-3-5-8/h1-5H,6-7,9H2 Y
  • Key:BHHGXPLMPWCGHP-UHFFFAOYSA-N Y
  (verify)

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][11][12] To a lesser extent, it also acts as a neurotransmitter in the human central nervous system.[13] In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation.[14] 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][15] Some authors have postulated that phenethylamine plays a role in affection without substantiating these claims with any direct evidence.[16][17]

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.

  1. ^ 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).
  2. ^ Cite error: The named reference Human trace amines and hTAARs October 2016 review was invoked but never defined (see the help page).
  3. ^ a b c d e Cite error: The named reference Renaissance was invoked but never defined (see the help page).
  4. ^ a b c d Cite error: The named reference Vascular was invoked but never defined (see the help page).
  5. ^ a b c d e f g Wishart DS, Guo AC, Oler E, Wang F, Anjum A, Peters H, et al. "Showing metabocard for Phenylethylamine (HMDB0012275)". Human Metabolome Database, HMDB. 5.0.
  6. ^ 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.
  7. ^ Cite error: The named reference SSAO was invoked but never defined (see the help page).
  8. ^ Cite error: The named reference FMO was invoked but never defined (see the help page).
  9. ^ Cite error: The named reference FMO3 catecholamines was invoked but never defined (see the help page).
  10. ^ a b c d Cite error: The named reference PubChem was invoked but never defined (see the help page).
  11. ^ Cite error: The named reference PEA VMAT2 MEDRS review was invoked but never defined (see the help page).
  12. ^ Cite error: The named reference Miller was invoked but never defined (see the help page).
  13. ^ 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.
  14. ^ 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.
  15. ^ 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. doi:10.1016/S0022-3565(25)29682-3. PMID 4748552.
  16. ^ 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. Bibcode:1995JAChS.117.8204G. doi:10.1021/ja00136a019. ISSN 0002-7863.
  17. ^ 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.


Cite error: There are <ref group=note> tags on this page, but the references will not show without a {{reflist|group=note}} template (see the help page).

This article is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.