Phenethylamine

Phenethylamine, or β-Phenylethylamine (2-Phenylethylamine), is an alkaloid and monoamine. Phenethylamine has also structural isomer α- or 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 suggested that phenethylamine from food may have psychoactive effects in sufficient quantities. However, it is quickly metabolized by the enzyme MAO-B, preventing significant concentrations from reaching the brain.

Substituted phenethylamines are a broad and diverse class of compounds that include neurotransmitters, hormones, stimulants, hallucinogens, entactogens, anorectics, bronchodilators, and antidepressants.

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Chemistry

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

Infusion of PEA increased extracellular levels of dopamine^[2] while at the same time inhibiting DA neuron firings.^[3][4] It also modulates noradrenergic transmission.^[5] It has GABAergic antagonism.^[6]

Low levels are found in ADHD^[7] and often in depression, while levels are elevated in schizophrenia.^[8] This is associated with low dopamine in ADHD and depression and high dopamine in schizophrenia.

Chocolate theory of love

In the early 1980s, chemistry of love researcher Michael Libowitz, 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."^[9] 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

Substituted phenethylamines carry additional chemical modifications at the phenyl ring, the sidechain, 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

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

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 part to the pioneering work of Alexander Shulgin, much of which is described in the book PiHKAL.

Graphical overview

See also

• Catecholamines
• PiHKAL
• Alexander Shulgin
• Phenethyl alcohol
• 2C's

References