Phenethylamine
Encyclopedia
Phenylethylamine or phenethylamine (PEA) is a natural
monoamine alkaloid
, trace amine
, and also the name of a class of chemicals with many members well known for psychoactive drug
and stimulant
effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter
in the mammalian central nervous system
. It is biosynthesized from the amino acid
phenylalanine
by enzymatic decarboxylation
. Besides 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 is usually inactive
on account of extensive first-pass metabolism by monoamine oxidase
(MAO) into phenylacetic acid
, preventing significant concentration
s from reaching the brain
.
The group of phenethylamine derivatives
is referred to as the phenethylamines. Substituted phenethylamine
s, substituted amphetamine
s, and substituted methylenedioxyphenethylamines (MDxx) are a series of broad and diverse classes of compounds derived from phenethylamine that include stimulant
s, psychedelics
, and entactogens, as well as anorectic
s, bronchodilator
s, decongestant
s, and antidepressant
s, among others.
, and ether
. 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.
Phenethylamine has an inactive constitutional isomer 1-phenylethylamine
, which itself has two stereoisomers: (R)-(+)-1-phenylethylamine
and (S)-(-)-1-phenylethylamine.
norepinephrine
and dopamine
. However when taken orally it is rapidly metabolized.
Abnormally low concentrations of endogenous phenethylamine are found in those suffering from attention-deficit hyperactivity disorder
(ADHD) and often in clinical depression
, whereas abnormally high concentrations have been discovered to have a strong, positive correlation with the incidence of schizophrenia
.
Phenylethylamine is metabolized by MAO-A, MAO-B, aldehyde dehydrogenase
, and dopamine-beta-hydroxylase.
When initial phenylethylamine brain concentration are low, phenylethylamine brain levels can be increased by a 1000-fold when taking a MAO Inhibitor, and by 3-4 times when the initial concentration are high.
Alcohol and THC increase phenylethylamine levels by a 4-fold.
, 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 and then by magazine free-lancers, evolving into the now-eponymous "chocolate theory of love." 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 a monoamine oxidase inhibitor
(MAOI).
Natural product
A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design...
monoamine alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
, trace amine
Trace amine
Trace amines are endogenous compounds structurally related to classical biogenic amines, such as catecholamines, serotonin and histamine. Trace amines include p-tyramine, β-phenylethylamine, tryptamine, octopamine, and 3-iodothyronamine, and are found in the nervous systems of animals from insects...
, and also the name of a class of chemicals with many members well known for psychoactive drug
Psychoactive drug
A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...
and stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
in the mammalian central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
. It is biosynthesized from the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
by enzymatic decarboxylation
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
. Besides mammals, phenethylamine is found in many other organisms and foods such as chocolate
Chocolate
Chocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...
, especially after microbial
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...
fermentation
Fermentation (food)
Fermentation in food processing typically is the conversion of carbohydrates to alcohols and carbon dioxide or organic acids using yeasts, bacteria, or a combination thereof, under anaerobic conditions. Fermentation in simple terms is the chemical conversion of sugars into ethanol...
. It is sold as a dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
for purported mood
Mood (psychology)
A mood is a relatively long lasting emotional state. Moods differ from emotions in that they are less specific, less intense, and less likely to be triggered by a particular stimulus or event....
and weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
-related therapeutic benefits; however, orally
Oral administration
Oral administration is a route of administration where a substance is taken through the mouth.-Terminology:Per os is an adverbial phrase meaning literally from Latin "by mouth" or "by way of the mouth." The expression is used in medicine to describe a treatment that is taken orally. The...
ingested phenethylamine is usually inactive
Activity (chemistry)
In chemical thermodynamics, activity is a measure of the “effective concentration” of a species in a mixture, meaning that the species' chemical potential depends on the activity of a real solution in the same way that it would depend on concentration for an ideal solution.By convention, activity...
on account of extensive first-pass metabolism by monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
(MAO) into phenylacetic acid
Phenylacetic acid
Phenylacetic acid is an organic compound containing a phenyl functional group and a carboxylic acid functional group. It is a white solid with a disagreeable odor...
, preventing significant concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
s from reaching the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
.
The group of phenethylamine derivatives
Derivative (chemistry)
In chemistry, a derivative is a compound that is derived from a similar compound by some chemical or physical process. In the past it was also used to mean a compound that can be imagined to arise from another compound, if one atom is replaced with another atom or group of atoms, but modern...
is referred to as the phenethylamines. Substituted phenethylamine
Substituted phenethylamine
The substituted phenethylamines are chemical compounds with the 2-phenethylamine chemical structure modified at the phenyl ring, sidechain, and/or amino group. Some of them are psychoactive drugs, including stimulants, psychedelics, opioids, and entactogens, which exert their effects primarily...
s, substituted amphetamine
Substituted amphetamine
Substituted amphetamines are a chemical class of stimulants, entactogens, hallucinogens, and other drugs. They feature a phenethylamine core with a methyl group attached to the alpha carbon resulting in amphetamine, along with additional substitutions...
s, and substituted methylenedioxyphenethylamines (MDxx) are a series of broad and diverse classes of compounds derived from phenethylamine that include stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
s, psychedelics
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...
, and entactogens, as well as anorectic
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
s, bronchodilator
Bronchodilator
A bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs. Bronchodilators may be endogenous , or they may be medications administered for the treatment of breathing difficulties...
s, decongestant
Decongestant
A decongestant or nasal decongestant is a type of drug that is used to relieve nasal congestion.-Pharmacology:The vast majority of decongestants act via enhancing norepinephrine and epinephrine or adrenergic activity by stimulating the α-adrenergic receptors...
s, and antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
s, among others.
Chemistry
Phenethylamine is an amine, consisting of a benzene ring and an aminoethyl group. It is a colorless liquid at room temperature. Phenethylamine is soluble in water, ethanolEthanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, and ether
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
. Similar to other low-molecular-weight amines, it has a fishy odor. Upon exposure to air, it forms a solid carbonate
Carbonate
In chemistry, a carbonate is a salt of carbonic acid, characterized by the presence of the carbonate ion, . The name may also mean an ester of carbonic acid, an organic compound containing the carbonate group C2....
salt
Salt
In chemistry, salts are ionic compounds that result from the neutralization reaction of an acid and a base. They are composed of cations and anions so that the product is electrically neutral...
with carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
. Phenethylamine is strongly basic
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
and forms a stable crystalline hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
salt with a melting point of 217 °C. Phenethylamine is also a skin irritant and possible sensitizer.
Phenethylamine has an inactive constitutional isomer 1-phenylethylamine
1-Phenylethylamine
1-Phenylethylamine is a monoamine compound. Individual enantiomers of this basic compound are useful for performing chiral resolution of acidic compounds by forming diastereomeric salts....
, which itself has two stereoisomers: (R)-(+)-1-phenylethylamine
1-Phenylethylamine
1-Phenylethylamine is a monoamine compound. Individual enantiomers of this basic compound are useful for performing chiral resolution of acidic compounds by forming diastereomeric salts....
and (S)-(-)-1-phenylethylamine.
Pharmacology
Phenethylamine, similar to amphetamine in its action, releasesReleasing agent
A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...
norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
. However when taken orally it is rapidly metabolized.
Abnormally low concentrations of endogenous phenethylamine are found in those suffering from attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
(ADHD) and often in clinical depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, whereas abnormally high concentrations have been discovered to have a strong, positive correlation with the incidence of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
Pharmacokinetics
Phenylethylamine's half-life is 5–10 minutes.Phenylethylamine is metabolized by MAO-A, MAO-B, aldehyde dehydrogenase
Aldehyde dehydrogenase
Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation of aldehydes.- Function :Aldehyde dehydrogenase is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids, which leave the liver and are metabolized by the body’s muscle and heart...
, and dopamine-beta-hydroxylase.
When initial phenylethylamine brain concentration are low, phenylethylamine brain levels can be increased by a 1000-fold when taking a MAO Inhibitor, and by 3-4 times when the initial concentration are high.
Alcohol and THC increase phenylethylamine levels by a 4-fold.
Chocolate theory of love
In the early 1980s, researcher Michael LiebowitzMichael Liebowitz
Dr. Michael R. Liebowitz is a Columbia University psychiatrist and founder of the Anxiety Disorders Clinic, the first of its kind, at the New York State Psychiatric Institute. In 1985, he researched and highlighted an underrecognized status of Social Anxiety Disorder . This led to subsequent...
, author of the popular 1983 book The Chemistry of Love, remarked to reporters that "chocolate
Chocolate
Chocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...
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 and then by magazine free-lancers, evolving into the now-eponymous "chocolate theory of love." 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 a monoamine oxidase inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
(MAOI).
See also
- 1-Phenylethylamine1-Phenylethylamine1-Phenylethylamine is a monoamine compound. Individual enantiomers of this basic compound are useful for performing chiral resolution of acidic compounds by forming diastereomeric salts....
- AmphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
- Alexander ShulginAlexander ShulginAlexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...
- PiHKALPiHKALPiHKAL: A Chemical Love Story is a book by Dr. Alexander Shulgin and Ann Shulgin which was published in 1991. The subject of the work is psychoactive phenethylamine chemical derivatives, notably those that act as psychedelics and/or empathogen-entactogens...
- Substituted phenethylamineSubstituted phenethylamineThe substituted phenethylamines are chemical compounds with the 2-phenethylamine chemical structure modified at the phenyl ring, sidechain, and/or amino group. Some of them are psychoactive drugs, including stimulants, psychedelics, opioids, and entactogens, which exert their effects primarily...
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