User:Mark PEA/Phenethylamine
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| Names | |
|---|---|
| IUPAC name
2-Phenylethylamine
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| Other names
Phenethylamine
β-Phenylethylamine 2-Phenyl-1-aminoethane β-Aminoethylamine 2-Phenylethanamine | |
| Identifiers | |
3D model (JSmol)
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| UNII | |
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| Properties | |
| C8H11N | |
| Molar mass | 121.18 g/mol |
| Density | 0.964 g/cm3 |
| Melting point | -60 °C |
| Boiling point | 194.5-195 °C |
| Hazards | |
| NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Phenethylamine, or β-Phenylethylamine (2-Phenylethylamine), is an alkaloid and monoamine. Phenethylamine also has a constitutional isomer α-Phenylethylamine (1-Phenylethylamine), which has two stereoisomers: (R)-(+)-1-phenylethylamine and (S)-(-)-1-phenylethylamine. In the human brain, 2-phenethylamine is believed to function as a neuromodulator or neurotransmitter (trace amine). Phenethylamine is a natural compound biosynthesized from the amino acid phenylalanine by enzymatic decarboxylation. It is also found in many foods such as chocolate, especially after microbial fermentation. It has been shown that phenylethylamine as a supplement in doses of roughly 1-2 grams has psychoactive effects.[2]
Substituted phenethylamines are a broad and diverse class of compounds that include stimulants, hallucinogens, entactogens, anorectics, bronchodilators, and antidepressants.
Chemistry
[edit]Phenethylamine (PEA) is an aromatic amine, which is a colorless liquid at room temperature. It is soluble in water, ethanol, and ether.[1] 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.
Neurochemistry
[edit]Infusion of PEA increased extracellular levels of dopamine[3] while at the same time inhibiting DA neuron firings.[4][5] It also modulates noradrenergic transmission.[6] It has GABAergic antagonism.[7]
Low levels are found in ADHD[8] and often in depression, while levels are elevated in schizophrenia.[9] This is associated with low dopamine in ADHD and depression and high dopamine in schizophrenia.
Chocolate theory of love
[edit]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, then by magazine free-lancers, and evolved into the now-eponymous "chocolate theory of love."[10] 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.
Substituted phenethylamines
[edit]
Substituted phenethylamines carry additional chemical modifications at the phenyl ring, the side chain, or the amino group:
- Substituted Amphetamines are homologues of phenethylamines carrying an alpha-methyl (α-CH3) group at the sidechain carbon atom next to the amino group.
- Catecholamines are phenethylamines carrying two hydroxy groups in positions 3 and 4 of the phenyl ring. Examples are the hormones and neurotransmitters dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline).
- The aromatic amino acids phenylalanine and tyrosine are phenethylamines carrying a carboxyl group (COOH) in alpha position.
- 2Cs are phenethylamines with methoxy groups attached to the 2 and 5 carbons and no alpha-methyl group.
Pharmacology
[edit]Phenylethylamine's half life is 5-10 minutes.[2] Phenylethylamine is metabolized by MAO-B, aldehyde dehydrogenase, MAO-A, and dopamine-beta-hydroxylase.[2] Phenylethylamine brain levels can be increased by a 1000 fold when taking an MAO Inhibitor and 3-4 times when taken by itself.[11] Alcohol and THC increase PEA levels by a 4 fold.[11]
Many substituted phenethylamines are pharmacologically active drugs due to their similarity to the monoamine neurotransmitters:
- Stimulants like the plant alkaloids ephedrine and cathinone and the synthetic drug dextroamphetamine and methylphenidate
- Hallucinogens like the plant alkaloid mescaline and the synthetic drug 2C-B
- Empathogen-entactogens like MDMA (ecstasy) and MDA
- Anorectics like phentermine, fenfluramine, and amphetamine
- Bronchodilators like salbutamol and ephedrine
- Antidepressants like venlafaxine, bupropion and the monoamine oxidase inhibitors phenelzine and tranylcypromine.
Substitution table
[edit]Some of the more important phenethylamines are tabulated below. For simplicity, the stereochemistry of the sidechain is not covered in the table. Hundreds of other simple synthetic phenethylamines are known. This is due in large part to the pioneering work of Alexander Shulgin, much of which is described in the book PiHKAL (Phenethylamines i Have Known And Loved).
| Short Name | Rα | Rβ | R2 | R3 | R4 | R5 | RN | Full Name |
|---|---|---|---|---|---|---|---|---|
| Tyramine | OH | 4-hydroxy-phenethylamine | ||||||
| Dopamine | OH | OH | 3,4-dihydroxy-phenethylamine | |||||
| Epinephrine (Adrenaline) | OH | OH | OH | CH3 | β,3,4-trihydroxy-N-methylphenethylamine | |||
| Norepinephrine (Noradrenaline) | OH | OH | OH | β,3,4-trihydroxyphenethylamine | ||||
| Phenylephrine | OH | OH | CH3 | β,3-dihydroxy-N-methylphenethylamine | ||||
| 6-Hydroxydopamine | OH | OH | OH | 2,4,5-trihydroxyphenethylamine | ||||
| Salbutamol | OH | OH | CH2OH | C(CH3)3 | β,4-dihydroxy-3-hydroxymethyl-N-tert-butyl-phenethylamine | |||
| Beta-methyl-phenethylamine | CH3 | β-methylphenethylamine | ||||||
| Amphetamine | CH3 | α-methylphenethylamine | ||||||
| Methamphetamine | CH3 | CH3 | N-methylamphetamine | |||||
| Methylphenidate | N,α-butylene-β-methoxycarbonylphenethylamine | |||||||
| Ephedrine, pseudoephedrine |
CH3 | OH | CH3 | N-methyl-β-hydroxyamphetamine | ||||
| Acetylamphetamine | CH3 | COCH3 | α-methyl-3-acetylphenethylamine | |||||
| Cathine | CH3 | OH | β-hydroxy-amphetamine | |||||
| Cathinone | CH3 | =O | β-ketoamphetamine | |||||
| Methcathinone | CH3 | =O | CH3 | N-methyl-β-ketoamphetamine | ||||
| Bupropion | CH3 | =O | Cl | C(CH3)3 | 3-chloro-N-tert-butyl-β-ketoamphetamine | |||
| Fenfluramine | CH3 | CF3 | CH2CH3 | 3-trifluoromethyl-N-ethyl-amphetamine | ||||
| Phentermine | 2CH3 | α,α-dimethylphenethylamine | ||||||
| Mescaline | OCH3 | OCH3 | OCH3 | 3,4,5-trimethoxyphenethylamine | ||||
| MDA | CH3 | -O-CH2-O- | 3,4-methylenedioxyamphetamine | |||||
| MDMA | CH3 | -O-CH2-O- | CH3 | 3,4-methylenedioxy-N-methylamphetamine | ||||
| MDMC | CH3 | =O | -O-CH2-O- | CH3 | 3,4-methylenedioxy-N-methyl-β-ketoamphetamine | |||
| DOM | CH3 | OCH3 | CH3 | OCH3 | 2,5-dimethoxy-4-methylamphetamine | |||
| DOB | CH3 | OCH3 | Br | OCH3 | 2,5-dimethoxy-4-bromoamphetamine | |||
| DON | CH3 | OCH3 | NO2 | OCH3 | 2,5-dimethoxy-4-nitroamphetamine | |||
| 2C-B | OCH3 | Br | OCH3 | 2,5-dimethoxy-4-bromophenethylamine | ||||
| 2C-C | OCH3 | Cl | OCH3 | 2,5-dimethoxy-4-chlorophenethylamine | ||||
| DOI | CH3 | OCH3 | I | OCH3 | 2,5-dimethoxy-4-iodoamphetamine | |||
| 2C-I | OCH3 | I | OCH3 | 2,5-dimethoxy-4-iodophenethylamine | ||||
| 2C-D | OCH3 | CH3 | OCH3 | 2,5-dimethoxy-4-methylphenethylamine | ||||
| 2C-E | OCH3 | CH2-CH3 | OCH3 | 2,5-dimethoxy-4-ethylphenethylamine | ||||
| 2C-F | OCH3 | F | OCH3 | 2,5-dimethoxy-4-fluorophenethylamine | ||||
| 2C-N | OCH3 | NO2 | OCH3 | 2,5-dimethoxy-4-nitrophenethylamine | ||||
| 2C-T-2 | OCH3 | S-CH2CH3 | OCH3 | 2,5-dimethoxy-4-ethylthio-phenethylamine | ||||
| 2C-T-4 | OCH3 | S-CH(CH3)2 | OCH3 | 2,5-dimethoxy-4-isopropylthio-phenethylamine | ||||
| 2C-T-7 | OCH3 | S-CH2CH2CH3 | OCH3 | 2,5-dimethoxy-4-propylthio-phenethylamine | ||||
| 2C-T-8 | OCH3 | S-CH2-C3H5 | OCH3 | 2,5-dimethoxy-4-cyclopropylmethylthio-phenethylamine | ||||
| 2C-T-9 | OCH3 | S-C(CH3)3 | OCH3 | 2,5-dimethoxy-4-tert-butylthio-phenethylamine | ||||
| 2C-T-21 | OCH3 | S-CH2-CH2-F | OCH3 | 2,5-dimethoxy-4-(2-fluoroethylthio)-phenethylamine | ||||
| Short Name | Rα | Rβ | R2 | R3 | R4 | R5 | RN | Full Name |
Relation to amphetamine
[edit]Despite the negative stigma tagged to amphetamine (alpha-methylphenethylamine) ("speed", "amp", "uppers") and methylamphetamine (N-methyl-alpha-methylphenethylamine) ("speed", "meth", "ice", "crystal") and it's recreational compounds, the phenylethylamine comprises not only these so called toxic or dangerous amphetamine or methamphetamine, it makes up many drugs with important uses including medical ones like bronchodilators; used for dilating or "opening" the bronchi and bronchioles, which is benefit to and can save the life of an asthmatic (with salbutamol or albuterol or epinephrin for someone with life-threatening allergic reactions), important neurotransmitters like dopamine, epinephrine (Adrenaline), (which humans depend on for normal functioning and survival), and some medically used stimulants like amphetamine (Adderall, Dexedrine), methylamphetamine (Desoxyn), methylphenidate (Ritalin, Concerta and others); which benefit people with ADHD and ADD (attention and behavioral disorders affecting many children and some adults), narcolepsy (person with insomnia that can fall asleep at anytime during the day), chronic fatigue syndrome(CFS), syndrome that inflicts unexplainable pain, fatigue, interruption of normal sleep, cognitive impairments (confusion, forgetfulness, and a cloudy mental or head feeling), ataxia, nausea and gastrointestinal problems like IBS and other negative symptoms, and can be used for traumatic brain injury (TBS). The majority of phenylethylamines used by many have some or all of the actions of the stigmatized amphetamine and methamphetamine (though sometimes they lack the recreational abuse) and also share great structural similarity to methamphetamine and amphetamine.
Graphical overview
[edit]
See also
[edit]References
[edit]- ^ a b Merck Index, 12th Edition, 7371.
- ^ a b c Sabelli, Hector C. (1995). "Phenylethylamine modulation of affect: therapeutic and diagnostic implications". J Neuropsychiatry Clin Neurosci. 7: 6–14. PMID 7711493.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Nakamura, Ishii, Nakahara. "Characterization of β-phenylethylamine-induced monoamine release in rat nucleus accumbens : a microdialysis study". European journal of pharmacology.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Kota Ishida, Mikio Murata; et al. (2005). "Effects of -Phenylethylamine on Dopaminergic Neurons of the Ventral Tegmental Area in the Rat: A Combined Electrophysiological and Microdialysis Study". Journal of Pharmacology and Experimental Therapeutics Fast Forward. 314: 916. doi:10.1124/jpet.105.084764. PMID 15879004.
{{cite journal}}: Explicit use of et al. in:|author=(help) - ^ EM Parker and LX Cubeddu. "Comparative effects of amphetamine, phenylethylamine and related drugs on dopamine efflux, dopamine uptake and mazindol binding" (abstract). PMID 3129549.
{{cite journal}}: Cite journal requires|journal=(help) - ^ I. A. Paterson (1993). "The potentiation of cortical neuron responses to noradrenaline by 2-phenylethylamine is independent of endogenous noradrenaline". Neurochemical Resarch. 18: 1329. doi:10.1007/BF00975055.
- ^ M Federici; et al. (2005). "Trace amines depress GABA B response in dopaminergic neurons by inhibiting G-betagamma-gated inwardly rectifying potassium channels" (abstract). Molecular Pharmacology. 67: 1283–1290. doi:10.1124/mol.104.007427. PMID 15644497.
{{cite journal}}: Explicit use of et al. in:|author=(help) - ^ Baker GB; et al. "Phenylethylaminergic mechanisms in attention-deficit disorder".
{{cite journal}}: Cite journal requires|journal=(help); Explicit use of et al. in:|author=(help) - ^ SG Potkin; et al. (1979). "Phenylethylamine in paranoid chronic schizophrenia". Science. 206: 470. doi:10.1126/science.504988. PMID 504988.
{{cite journal}}: Explicit use of et al. in:|author=(help) - ^ Liebowitz, Michael, R. (1983). The Chemistry of Love. Boston: Little, Brown, & Co.
- ^ a b Sabelli, Hector C. (1978). "Phenylethylamine and brain function". Biochem Pharmacol. 27 (13): 1707–1711. PMID 361043.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help)
External links
[edit]- Book II of PiHKAL online
- Review and summary of PiHKAL, including table of 300+ phenethylamines: ascii postscript
- A Structural Tour of PiHKAL
{{PiHKAL}} [[Category:Phenethylamines]] [[ca:Fenetilamina]] [[cs:Fenylethylamin]] [[de:Phenethylamin]] [[es:Feniletilamina]] [[fr:Phényléthylamine]] [[hr:Feniletilamin]] [[it:Feniletilamina]] [[he:פנתילאמין]] [[nl:Fenylethylamine]] [[ja:フェネチルアミン]] [[pl:Fenyloetyloamina]] [[ru:Фенилэтиламин]] [[sk:Fenyletylamín]] [[fi:Fenetyyliamiini]] [[sv:Fenetylamin]] [[zh:苯乙胺]]