Phenethylamine

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Phenethylamine[1]
IUPAC name	2-Phenylethylamine
Other names	Phenethylamine β-Phenylethylamine 2-Phenyl-1-aminoethane 2-Phenylethanamine
Identifiers
CAS number	[64-04-0]
PubChem	1001
SMILES	c1ccccc1CCN
ChemSpider ID	13856352
Properties
Molecular formula	C8H11N
Molar mass	121.18 g/mol
Density	0.964 g/cm3
Melting point	-60 °C
Boiling point	194.5-195 °C
Hazards
MSDS	MSDS for phenethylamine
NFPA 704	2 2 2
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references

Phenethylamine, or β-phenylethylamine or 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. However trace amounts from food are quickly metabolized by the enzyme MAO-B, preventing significant concentrations from reaching the brain.^[2][3]

Phenylethylamine is a precursor to the neurotransmitter phenylethanolamine.^[4]

D-Phenylalanine increases the brain content of phenylethylamine.^[5] Phenylethylamine has been shown at least indirectly to satisfy the four main criteria required to demonstrate that a neuroamine sustains mood and that its deficit can be responsible for depression.^[5] Antidepressant drug therapy is an indirect (pharmacological) "replacement" of brain phenylethylamine.^[5]

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

[edit] Chemistry

Phenethylamine 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.

[edit] Neurochemistry

Infusion of phenylethylamine increases extracellular levels of dopamine^[6] while at the same time inhibiting DA neuron firings.^[7][8] It also modulates noradrenergic transmission.^[9] Phenethylamine, along with tyramine, reversibly depresses the slow GABA_B receptor inhibitory post-synaptic potential in midbrain dopaminergic cells.^[10]

Low levels are found in those suffering from attention deficit disorder^[11] and often in depression, while levels are elevated in schizophrenia.^[12] This is associated with low dopamine in ADHD and depression and high dopamine in schizophrenia.

[edit] Chocolate theory of love

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."^[13] 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 without the use of an MAOI (monoamine oxidase inhibitor).

[edit] Substituted phenethylamines

General structure of phenethylamines and amphetamines (see the table below).

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.

[edit] Pharmacology

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Phenylethylamine's half life is 5-10 minutes.^{[14][dubious – discuss]} Phenylethylamine is metabolized by MAO-A ^[3], MAO-B ^[2], aldehyde dehydrogenase and dopamine-beta-hydroxylase.^[14] Phenylethylamine brain levels can be increased by a 1000 fold when taking an MAO Inhibitor and 3-4 times when taken by itself.^{[15][dubious – discuss]} Alcohol and THC increase phenylethylamine levels by a 4 fold.^{[15][dubious – discuss]}

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.

[edit] 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 large part to the pioneering work of Alexander Shulgin, much of which is described in the book PiHKAL (Phenethylamines i Have Known And Loved).

[edit] Relation to amphetamine

Despite the negative stigma tagged to amphetamine (alpha-methylphenethylamine) ("speed", "amp", "uppers") and methylamphetamine (N-methyl-alpha-methylphenethylamine) ("speed", "meth", "ice", "crystal") and its recreational compounds, the phenylethylamines comprise amphetamine and methamphetamine, and make up many drugs with important uses including the bronchodilators. These are used for dilating or "opening" the bronchi and bronchioles, which is of benefit to, and can save the life of, an asthmatic (with salbutamol or albuterol or adrenaline for someone with life-threatening allergic reactions).

The phenethylamines also include 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 (the sudden, irresistable urge to fall asleep at any time regardless of how much sleep you have had the night before) and chronic fatigue syndrome (CFS).

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.

[edit] Graphical overview

[edit] See also

• Catecholamines
• Alexander Shulgin
  • PiHKAL (Phenethylamines i Have Known And Loved)
• Phenethyl alcohol
• 2C's

[edit] References

[edit] External links

• Book II of PiHKAL online
• Phenethylamine entry in PiHKAL • info
• Review and summary of PiHKAL, including table of 300+ phenethylamines: ascii postscript
• A Structural Tour of PiHKAL