Phenethylamine

Effects

Shulgin notes

These figures come from the Shulgins' own small trials, published decades ago. They are history, not a dosing guide: they were never checked the way a harm reduction dose table is, and batches, purity and people differ.

Book

PiHKAL (1991), entry #142

Dose listed

>1,600 mg orally WP

Duration listed

Unknown WP

Read entry #142 in Erowid's online library

From PiHKAL and TiHKAL by Alexander and Ann Shulgin, as tabulated in Wikipedia's articles on the books (CC BY-SA 4.0). The books' text belongs to the Shulgins, so only the listed figures and a link are given here. Synthesis details are never shown on this site.

Overview

Phenethylamine (also called PEA, β-phenylethylamine, β-phenethylamine, or benzeneethanamine) is a trace amine and influencer of many neurotransmitters, such as dopamine and serotonin. Phenethylamine is an important molecule in the brain, but is not often used as a supplement because it is rapidly broken down into inactive components before it is able to reach and cross the blood-brain barrier.[1] PW

Organic compound, which is a name of a class of chemicals that are quite well known for psychoactive and/or stimulant effects. Normally not used as a supplement as it is rapidly broken down into inactive compounds. Is found in many foods. TS

Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.[2–7] WP

Phenethylamine is sold as a dietary supplement for purported mood and weight loss-related therapeutic benefits; however, in orally ingested phenethylamine, a significant amount is metabolized in the small intestine by monoamine oxidase B (MAO-B) and then aldehyde dehydrogenase (ALDH), which converts it to phenylacetic acid. This means that for significant concentrations to reach the brain, the dosage must be higher than for other methods of administration. Some authors have postulated that phenethylamine plays a role in affection without substantiating these claims with any direct evidence.[8–12] WP

Phenethylamines, or more properly, substituted phenethylamines, are the group of phenethylamine derivatives that contain phenethylamine as a "backbone"; in other words, this chemical class includes derivative compounds that are formed by replacing one or more hydrogen atoms in the phenethylamine core structure with substituents. The class of substituted phenethylamines includes all substituted amphetamines, and substituted methylenedioxyphenethylamines (MDxx), and contains many drugs which act as empathogens, stimulants, psychedelics, anorectics, bronchodilators, decongestants, and/or antidepressants, among others. WP

History

History

Phenethylamine was first isolated and identified by Marceli Nencki in 1876. Subsequently, it was first synthesized by Treat B. Johnson and Herbert H. Guest in 1909.[13–17] WP

Legal status

• In most countries, phenethylamine is easily accessible. It is sold as a dietary supplement for purported mood- and weight loss-related therapeutic benefits. PW

United states

Phenylethylamine is not a scheduled substance in the United States. However, at least one person in the United States has been prosecuted under the Federal Analogue Act for selling phenylethylamine with the prosecutions argument that PEA is a structural analog of amphetamine and methamphetamine.[18][19][20] WP

Pharmacology

Detection in body fluids

Reviews that cover attention deficit hyperactivity disorder (ADHD) and phenethylamine indicate that several studies have found abnormally low urinary phenethylamine concentrations in ADHD individuals when compared with controls. In treatment-responsive individuals, amphetamine and methylphenidate greatly increase urinary phenethylamine concentration. An ADHD biomarker review also indicated that urinary phenethylamine levels could be a diagnostic biomarker for ADHD.[21] WP

Thirty minutes of moderate- to high-intensity physical exercise has been shown to induce an 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 -phenylalanine by aromatic amino acid decarboxylase at approximately the same rate as dopamine is produced. Monoamine oxidase 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 completely deaminated in the gut as it is a selective substrate for MAO-B, which is not primarily 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. 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. 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.[7][22–25] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

Skydiving has also been shown to induce a marked increase in urinary phenethylamine concentrations.[26][27] WP

Monoamine releasing agent

Phenethylamine, being similar to amphetamine in its action at their common biomolecular targets, is a releasing agent of norepinephrine and dopamine. It is roughly equipotent to amphetamine in this regard in vitro. Phenethylamine is inactive as a psychostimulant under normal circumstances due to rapid metabolism by monoamine oxidase (MAO), but can become active in the presence of a monoamine oxidase inhibitor (MAOI).[4][5][28][29] WP

TAAR1 agonist

Phenethylamine is a potent agonist of the mouse, rat, and human trace amine-associated receptor 1 (TAAR1). β-PEA is also an odorant binding TAAR4 in mice thought to mediate predator avoidance. Similarly to the case of amphetamine, phenethylamine shows enhanced locomotor stimulation, a psychostimulant-like effect, in TAAR1 knockout mice.[30–33] WP

Monoaminergic activity enhancer

Phenethylamine is a monoaminergic activity enhancer (MAE) of serotonin, norepinephrine, and dopamine in addition to its catecholamine-releasing activity. That is, it enhances the action potential-mediated release of these monoamine neurotransmitters. The compound is active as a MAE at much lower concentrations than the concentrations at which it induces the release of catecholamines. The MAE actions of phenethylamine and other MAEs may be mediated by TAAR1 agonism. Synthetic and more potent MAEs like phenylpropylaminopentane (PPAP) and selegiline (L-deprenyl) have been derived from phenethylamine.[34–38] WP

Other activities

Unlike its derivatives norepinephrine (noradrenaline) and epinephrine (adrenaline), phenethylamine is inactive as an agonist of the α- and β-adrenergic receptors.[39] WP

Pharmacokinetics

By oral route, phenethylamine's half-life is 5–10 minutes; endogenously produced PEA in catecholamine neurons has a half-life of roughly 30 seconds. In humans, PEA is metabolized by phenylethanolamine N-methyltransferase (PNMT), monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), the semicarbazide-sensitive amine oxidases (SSAOs) AOC2 and AOC3, flavin-containing monooxygenase 3 (FMO3), and aralkylamine N-acetyltransferase (AANAT). N-Methylphenethylamine, an isomer of amphetamine, is produced in humans via the metabolism of phenethylamine by PNMT. β-Phenylacetic acid is the primary urinary metabolite of phenethylamine and is produced via monoamine oxidase metabolism and subsequent aldehyde dehydrogenase metabolism. Phenylacetaldehyde is the intermediate product which is produced by monoamine oxidase and then further metabolized into β-phenylacetic acid by aldehyde dehydrogenase.[8][9][10][22][25][26][40–45] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

When the initial phenylethylamine concentration in the brain 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.[46] WP

Chemistry

Formula

C8H11N PC

CAS number

64-04-0 PC

Molar mass (g/mol)

121.18 PC

IUPAC name (computed by PubChem)

2-phenylethanamine PC

SMILES

C1=CC=C(C=C1)CCN PC

InChIKey

BHHGXPLMPWCGHP-UHFFFAOYSA-N PC

PubChem CID

1001

IUPAC name

2-Phenylethan-1-amine WP

Pop culture

No references added yet.

References

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