Phenethylamine /fÉ›nˈɛθəlÉ™miËn/ (PEA), β-phenethylamine, or phenylethylamine is an organic compound and a 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 neuromodulator or neurotransmitter in the mammalian central nervous system. It is biosynthesized from the amino acid L-phenylalanine by enzymatic decarboxylation via the enzyme aromatic L-amino acid decarboxylase. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after 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), which turns 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.
Occurrence
Phenethylamine is widely distributed throughout the plant kingdom and also present in animals, such as humans.
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. 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. Its density is 0.964 g/ml and its boiling point is 195 °C.
Synthesis
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.
Pharmacology
Phenethylamine, being similar to amphetamine in its action at their common biomolecular targets, releases norepinephrine and dopamine.
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 24Â hour urinary phenylacetic acid concentration following just 30Â 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 30Â 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.
Pharmacokinetics
By oral route, phenylethylamine's half-life is 5â€"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, aldehyde dehydrogenase and dopamine-beta-hydroxylase. N-methylphenethylamine, an isomer of amphetamine, is produced when phenethylamine is used as a substrate 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 3â€"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.
Toxicity
Acute toxicity studies on phenethylamine show an LD50 = 100Â mg/kg, after intravenous administration to mice. Consumption of large quantities by mice has been associated with Parkinson's disease-like neurological deficits.
See also
References
External links
- Phenethylamine MS Spectrum