|Systematic (IUPAC) name|
None (without an MAO-B inhibitor)
Moderate (with an MAO-B inhibitor)
|Metabolism||MAO-A, SSAOs, PNMT, AANAT, FMO3, and others|
Exogenous: 5–10 minutes
Endogenous: ~30 seconds
|CAS Registry Number|
|Molecular mass||121.18 g/mol|
|Melting point||−60 °C (−76 °F) |
|Boiling point||197.5 °C (387.5 °F) |
Phenethylamine (PEA), also known as β-phenylethylamine (β-PEA) and 2-phenylethylamine is an natural monoamine alkaloid, a trace amine, and also the name of a class of chemicals with many members that are well known for their psychoactive and stimulant effects.
Phenylethylamine functions as a monoaminergic microbial fermentation. It is sold as a dietary supplement for purported mood and weight loss-related therapeutic benefits; however, orally ingested phenethylamine experiences extensive first-pass metabolism by monoamine oxidase B (MAO-B) and then aldehyde dehydrogenase (ALDH), which metabolize it into phenylacetic acid. This prevents significant concentrations from reaching the brain when taken in low doses.
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 empathogens, stimulants, psychedelics, anxiolytics (hypnotics) and entactogens, as well as anorectics, bronchodilators, decongestants, and antidepressants, among others.
- Natural occurrence 1
Physical and chemical properties 2
- Synthesis 2.1
- Pharmacodynamics 3.1
- Pharmacokinetics 3.2
- See also 4
- References 5
- External links 6
Phenethylamine is widely distributed throughout the plant kingdom and also present in animals, such as humans; it is also produced by certain fungi and bacteria (genus: Lactobacillus, Clostridium, Pseudomonas, and Enterobacteriaceae) and acts as a potent anti-microbial against certain pathogenic strains of Escherichia coli (e.g., the O157:H7 strain) at sufficient concentrations.
Physical and chemical properties
Phenethylamine is a primary amine, the amino-group being attached to a benzene ring through a two-carbon, or ethyl group. It is a colourless liquid at room temperature that has a fishy odour and is soluble in water, ethanol and ether. Its density is 0.964 g/ml and its boiling point is 195 °C. Upon exposure to air, it forms a solid carbonate salt with carbon dioxide. Phenethylamine is strongly basic, pKb = 4.17 (or pKa = 9.83), as measured using the HCl salt and forms a stable crystalline hydrochloride salt with a melting point of 217 °C.
One method for preparing β-phenethylamine, set forth in J. C. Robinson's and H. R. Snyder's Organic Syntheses (published 1955), involves the reduction of benzyl cyanide with hydrogen in liquid ammonia, in the presence of a Raney-Nickel catalyst, at a temperature of 130 °C and a pressure of 13.8 MPa. Alternative syntheses are outlined in the footnotes to this preparation.
A much more convenient method for the synthesis of β-phenethylamine is the reduction of ω-nitrostyrene by lithium aluminum hydride in ether, whose successful execution was first reported by R. F. Nystrom and W. G. Brown in 1948. Phenethylamine can also be produced via the cathodic reduction of benzyl cyanide in a divided cell.
Phenethylamine, being similar to amphetamine in its action at their common biomolecular targets, releases norepinephrine and dopamine. Phenethylamine also appears to induce acetylcholine release via a glutamate-mediated mechanism.
Reviews that cover attention deficit hyperactivity disorder (ADHD) and phenethylamine indicate that several studies have found abnormally low urinary phenethylamine content in ADHD individuals when compared with controls. In treatment responsive individuals, amphetamine and methylphenidate greatly increase urinary phenethylamine content. An ADHD biomarker review also indicated that urinary phenethylamine levels could be a diagnostic biomarker for ADHD.
Thirty minutes of moderate to high intensity physical exercise has been shown to induce an enormous increase in urinary phenylacetic acid, the primary metabolite of phenethylamine. Two reviews noted a study where the mean 24 hour urinary phenylacetic acid concentration following just 30 minutes of intense exercise rose 77% above its base level; the reviews suggest that phenethylamine synthesis sharply increases during physical exercise during which it is rapidly metabolized due to its short half-life of roughly 30 seconds. In a resting state, phenethylamine is synthesized in catecholamine neurons from L-phenylalanine by aromatic amino acid decarboxylase at approximately the same rate as dopamine is produced. Because of the pharmacological relationship between phenethylamine and amphetamine, the original paper and both reviews suggest that phenethylamine plays a prominent role in mediating the mood-enhancing euphoric effects of a runner's high, as both phenethylamine and amphetamine are potent euphoriants.
By oral route, phenylethylamine's half-life is 5–10 minutes; endogenously produced PEA in catecholamine neurons has a half-life of roughly 30 seconds. It is metabolized by phenylethanolamine N-methyltransferase, MAO-A, MAO-B, semicarbazide-sensitive amine oxidases (SSAOs), aldehyde dehydrogenase, and flavin-containing monooxygenase 3. N-methylphenethylamine, an isomer of amphetamine, is produced in humans via the metabolism of phenethylamine by phenylethanolamine N-methyltransferase. When the initial phenylethylamine brain concentration is low, brain levels can be increased 1000-fold when taking a monoamine oxidase inhibitor (MAOI), particularly a MAO-B inhibitor, and by 3–4 times when the initial concentration is high. β-Phenylacetic acid is the primary urinary metabolite of phenethylamine and is produced via monoamine oxidase metabolism.
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Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 220.127.116.11) (Berry, 2004) (Fig. 2) ... It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone ... Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut ...
Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life ...
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- Phenethylamine MS Spectrum