Phenethylamine

Structural formula
General
Surname	Phenethylamine
other names	β- phenylethylamine 2-phenylethylamine 2-phenyl-1-aminoethane
Molecular formula	C 8 H 11 N
Brief description	colorless liquid with an amine-like odor
External identifiers / databases
CAS number 64-04-0 EC number 200-574-4 ECHA InfoCard 100,000,523 PubChem 1001 ChemSpider 13856352 DrugBank DB04325 Wikidata Q407411
properties
Molar mass	121.18 g mol −1
Physical state	liquid
density	0.96 g cm −3 (20 ° C)
Melting point	<−60 ° C
boiling point	200-202 ° C
Vapor pressure	40 Pa (20 ° C)
solubility	poor in water (4.3 g l −1 at 20 ° C)
Refractive index	1.5290 (25 ° C)
safety instructions
GHS labeling of hazardous substances danger H and P phrases H: 290-301-314 P: 280-301 + 330 + 331-305 + 351 + 338-308 + 310
Toxicological data	200 mg · kg -1 ( LD 50 ,  guinea pigs ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Phenethylamine (also β- phenylethylamine (PEA) or with the correct chemical name 2-phenylethylamine ) is a trace amine . It is the parent substance of the phenylethylamine group and is widespread in plants as a precursor to the benzylisoquinoline alkaloids .

Occurrence

Phenethylamine is found in bitter almond oil and cocoa beans and has also been found in the brain and urine. The biogenic amine phenethylamine as parent substance of the catecholamines and many psychedelic effective hallucinogens is associated with the emergence of pleasure and happiness sensations associated.

Extraction and presentation

Phenethylamine is a natural compound that is biosynthesized from the amino acid phenylalanine through enzymatic decarboxylation .

Technically, the compound can be obtained, inter alia, by catalytic hydrogenation of benzyl cyanide at temperatures of 130 ° C. and pressures of 140 bar over Raney nickel catalysts in liquid ammonia .

In another possible synthesis variant, benzaldehyde is condensed with nitromethane in a Henry reaction to form nitrostyrene . After its reduction (hydrogenation), phenethylamine is obtained.

chemistry

Phenethylamine

Structural consideration

Homologs : The next higher side chain homologs is the amphetamine (- β -ethyl versus isopropyl), further homologues are known. Mescaline is an example of a phenyl nucleus derivative (3,4,5-trimethoxy-substituted). Norepinephrine , for example, issimultaneouslysubstituted by thecore and side chains. In summary, these diverse structural variants are represented inthe phenylethylamine group of substances.

effect

Orally ingested PEA only has a psychoactive effect on people in very high doses or with an MAO-B inhibitor . Even at doses of 1600 mg orally or nasally and 50 mg intravenously there was no effect. The reason for this may be that PEA degrades quickly in the human and animal body. The biological half-life after ingestion is five to ten minutes. In the brain, phenethylamine has a half-life of around 30 seconds. In humans, phenethylamine is converted by phenylethanolamine-N-methyltransferase (PNMT), monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), semicarbazide-sensitive amine oxidases (SSAOs), flavin-containing monooxygenase 3 (FMO3 ), and the aralkylamine-N-acetyltransferase (AANAT, EC  2.3.1.87 ) is metabolized.

Patients taking a monoamine oxidase inhibitor (for the treatment of depression or Parkinson's disease ) should avoid the intake of PEA as this can lead to a sharp rise in blood pressure and headaches.

Biological importance

According to a study by the Department of Cell Biology and Neurobiology at Harvard Medical School, the urine of some predatory mammals contains increased amounts of phenethylamine. Certain prey animals (here: mice and rats) perceive the substance olfactorily and avoid areas contaminated with predatory mammalian urine.

Individual evidence

1. ↑ ^{a b c d e f g h} Entry on phenethylamine in the GESTIS substance database of the IFA , accessed on January 9, 2019 (JavaScript required)
2. ↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-34.
3. ↑ Entry on phenethylamine in the ChemIDplus database of the United States National Library of Medicine (NLM)
4. ↑ ^{a b c} Entry on Phenethylamine. In: Römpp Online . Georg Thieme Verlag, accessed on July 26, 2019.
5. ↑ JC Robinson Jr., HR Snyder: β-Phenylethylamine In: Organic Syntheses . 23, 1943, p. 71, doi : 10.15227 / orgsyn.023.0071 ( PDF ).
6. ↑ Alexander Shulgin , Ann Shulgin: PIHKAL - A Chemical Love Story. Transform Press, ISBN 0-9630096-0-5 , pp. 815ff
7. ↑ O. Suzuki, Y. Katsumata, M. Oya: Oxidation of beta-phenylethylamine by both types of monoamine oxidase: examination of enzymes in brain and liver mitochondria of eight species. In: Journal of neurochemistry Volume 36, Number 3, March 1981, pp. 1298-1301, PMID 7205271 .
8. ↑ HE Shannon, EJ Cone, D. Yousefnejad: Physiologic effects and plasma kinetics of beta-phenylethylamine and its N-methyl homolog in the dog. In: The Journal of pharmacology and experimental therapeutics. Volume 223, Number 1, October 1982, pp. 190-196, PMID 7120117 .
9. ^ ^{A b} Lindemann L, Hoener MC: A renaissance in trace amines inspired by a novel GPCR family . In: Trends Pharmacol. Sci. . 26, No. 5, 2005, pp. 274-281. doi : 10.1016 / j.tips.2005.03.007 . PMID 15860375 .
10. ^ Robert G. Pendleton, George Gessner, John Sawyer: Studies on lung N-methyltransferases, a pharmacological approach . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 313, No. 3, 1980, pp. 263-8. doi : 10.1007 / BF00505743 . PMID 7432557 .
11. ↑ Suzuki O, Katsumata Y, Oya M: Oxidation of beta-phenylethylamine by both types of monoamine oxidase: examination of enzymes in brain and liver mitochondria of eight species . In: J. Neurochem. . 36, No. 3, 1981, pp. 1298-301. doi : 10.1111 / j.1471-4159.1981.tb01734.x . PMID 7205271 .
12. ^ HY Yang, NH Neff: Beta-phenylethylamine: A specific substrate for type B monoamine oxidase of brain . In: The Journal of Pharmacology and Experimental Therapeutics . 187, No. 2, 1973, pp. 365-71. PMID 4748552 .
13. ↑ S. Kaitaniemi, H. Elovaara, K. Grön, H. Kidron, J. Liukkonen, T. Salminen, M. Salmi, S. Jalkanen, K. Elima: The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase . In: Cell. Mol. Life Sci. . 66, No. 16, 2009, pp. 2743-2757. doi : 10.1007 / s00018-009-0076-5 . PMID 19588076 . "The preferred in vitro substrates of AOC2 were found to be 2-phenylethylamine, tryptamine and p-tyramine instead of methylamine and benzylamine, the favored substrates of AOC3."
14. ↑ Krueger SK, Williams DE, Williams: Mammalian flavin-containing monooxygenases: structure / function, genetic polymorphisms and role in drug metabolism . In: Pharmacol. Ther. . 106, No. 3, June 2005, pp. 357-387. doi : 10.1016 / j.pharmthera.2005.01.001 . PMID 15922018 . PMC 1828602 (free full text). "The biogenic amines, phenethylamine and tyramine, are N-oxygenated by FMO to produce the N-hydroxy metabolite, followed by a rapid second oxygenation to produce the trans-oximes (Lin & Cashman, 1997a, 1997b). This stereoselective N-oxygenation to the trans-oxime is also seen in the FMO-dependent N-oxygenation of amphetamine (Cashman et al., 1999)… Interestingly, FMO2, which very efficiently N-oxygenates N-dodecylamine, is a poor catalyst of phenethylamine N-oxygenation. The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). "
15. ↑ EC 2.3.1.87 - aralkylamine N-acetyltransferase . Technical University of Braunschweig. July 2014. Retrieved November 10, 2014.
16. ↑ Jatrosom ( tranylcypromine ) specialist information , as of March 2005.
17. ↑ David M. Ferrero, Jamie K. Lemon, Daniela Fluegge, Stan L. Pashkovski, Wayne J. Korzan, Sandeep Robert Datta, Marc Spehr, Markus Fendt, and Stephen D. Liberles: Detection and avoidance of a carnivore odor by prey In : Proceedings of the National Academy of Sciences PNAS July 5, 2011 Vol. 108 No. 27 11235-11240.