Phenethylamine (PEA) is an
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
,
natural
Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans ar ...
monoamine alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of simila ...
, and
trace amine
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to th ...
, which acts as a
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
stimulant
Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
in humans. In the brain, phenethylamine regulates
monoamine neurotransmission by binding to
trace amine-associated receptor 1 (TAAR1) and inhibiting
vesicular monoamine transporter 2
The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...
(VMAT2) in monoamine
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa ...
s.
To a lesser extent, it also acts as a
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neu ...
in the human
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
.
In mammals, phenethylamine
is produced from the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
L-phenylalanine by the enzyme
aromatic L-amino acid decarboxylase
Aromatic L-amino acid decarboxylase (AADC or AAAD), also known as DOPA decarboxylase (DDC), tryptophan decarboxylase, and 5-hydroxytryptophan decarboxylase, is a lyase enzyme (), located in region 7p12.2-p12.1.
Mechanism
The enzyme uses pyri ...
via
enzymatic decarboxylation
Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...
.
In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as
chocolate
Chocolate is a food made from roasted and ground cacao seed kernels that is available as a liquid, solid, or paste, either on its own or as a flavoring agent in other foods. Cacao has been consumed in some form since at least the Olmec ci ...
, especially after
microbial
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
fermentation
Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food p ...
.
Phenethylamine is sold as a
dietary supplement
A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
for purported
mood and
weight loss
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...
-related
therapeutic benefit
Therapeutic effect refers to the response(s) after a treatment of any kind, the results of which are judged to be useful or favorable. This is true whether the result was expected, unexpected, or even an unintended consequence. An adverse effect (i ...
s; however, in
orally ingested phenethylamine, a significant amount is metabolized in the
small intestine
The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...
by
monoamine oxidase B (MAO-B) and then
aldehyde dehydrogenase (ALDH), which converts it to
phenylacetic acid.
This means that for significant
concentration
In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', ''number concentration'', ...
s to reach the
brain
A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...
, the dosage must be higher than for other methods of administration.
Some authors postulated its role in people's falling-in-love without substantiating it with any direct evidence.
Phenethylamines, or more properly,
substituted phenethylamines, are the group of phenethylamine
derivatives that contain phenethylamine as a "backbone"; in other words, this
chemical class Chemical classification systems attempt to classify elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classificati ...
includes
derivative
In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...
compounds that are formed by replacing one or more hydrogen atoms in the phenethylamine core structure with
substituent
A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as '' side ...
s. The class of
substituted phenethylamines includes all
substituted amphetamine
Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with s ...
s, and
substituted methylenedioxyphenethylamines (MDxx), and contains many drugs which act as
empathogens,
stimulant
Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
s,
psychedelics,
anorectics,
bronchodilators,
decongestants, and/or
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...
s, among others.
Natural occurrence
Phenethylamine is produced by a wide range of species throughout the plant and animal kingdoms, including humans;
it is also produced by certain
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
and
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
(genera: ''
Lactobacillus,
Clostridium
''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative a ...
,
Pseudomonas'' and the family
Enterobacteriaceae) and acts as a potent
antimicrobial against certain pathogenic strains of ''
Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'' (e.g., the
O157:H7 strain) at sufficient concentrations.
Chemistry
Phenethylamine is a primary amine, the amino-group being attached to a
benzene ring through a two-carbon, or
ethyl group
In organic chemistry, an ethyl group (abbr. Et) is an alkyl substituent with the formula , derived from ethane (). ''Ethyl'' is used in the International Union of Pure and Applied Chemistry's nomenclature of organic chemistry for a saturated ...
.
It is a colourless liquid at room temperature that has a fishy odor, and is soluble in water,
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
and
ether
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again ...
.
Its density is 0.964 g/ml and its boiling point is 195 °C.
Upon exposure to air, it combines with
carbon dioxide
Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is t ...
to form a solid
carbonate
A carbonate is a salt of carbonic acid (H2CO3), characterized by the presence of the carbonate ion, a polyatomic ion with the formula . The word ''carbonate'' may also refer to a carbonate ester, an organic compound containing the carbonate ...
salt
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...
.
Phenethylamine is strongly
basic, pK
b = 4.17 (or pK
a = 9.83), as measured using the HCl salt, and forms a stable crystalline
hydrochloride salt with a melting point of 217 °C.
Substituted derivatives
Substituted phenethylamines are a
chemical class Chemical classification systems attempt to classify elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classificati ...
of
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
s based upon the phenethylamine structure; the class is composed of all the
derivative
In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...
compounds of phenethylamine which can be formed by replacing, or
substituting, one or more
hydrogen atom
A hydrogen atom is an atom of the chemical element hydrogen. The electrically neutral atom contains a single positively charged proton and a single negatively charged electron bound to the nucleus by the Coulomb force. Atomic hydrogen cons ...
s in the phenethylamine core structure with
substituent
A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as '' side ...
s.
Many substituted phenethylamines are psychoactive drugs, which belong to a variety of different drug classes, including
central nervous system stimulants (e.g.,
amphetamine),
hallucinogens (e.g.,
2,5-dimethoxy-4-methylamphetamine
2,5-Dimethoxy-4-methylamphetamine (DOM; known as STP, standing for "Serenity, Tranquility and Peace") is a psychedelic and a substituted amphetamine. It was first synthesized by Alexander Shulgin, and later reported in his book '' PiHKAL: A Chemic ...
),
entactogens (e.g.,
3,4-methylenedioxyamphetamine),
appetite suppressant
An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic.
The term is (from the Greek ''ἀν-'' (an-) = "without" ...
s (e.g.
phentermine),
nasal decongestants and
bronchodilators (e.g.,
pseudoephedrine
Pseudoephedrine (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent in higher doses.
It was first charact ...
),
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...
s (e.g.
bupropion
Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...
),
antiparkinson agents (e.g.,
selegiline
Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or ...
), and
vasopressor
An antihypotensive agent, also known as a vasopressor agent or simply vasopressor, or pressor, is any substance, whether endogenous or a medication, that tends to raise low blood pressure. Some antihypotensive drugs act as vasoconstrictors to i ...
s (e.g.,
ephedrine
Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in ...
), among others. Many of these psychoactive compounds exert their pharmacological effects primarily by modulating
monoamine neurotransmitter systems; however, there is no mechanism of action or biological target that is common to all members of this subclass.
Numerous
endogenous
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell.
In contrast, exogenous substances and processes are those that originate from outside of an organism.
For example, ...
compounds – including
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s, monoamine neurotransmitters, and many
trace amine
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to th ...
s (e.g.,
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
,
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...
,
adrenaline
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands an ...
,
tyramine
Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood ...
, and others) – are substituted phenethylamines. Dopamine
is simply phenethylamine with a hydroxyl group attached to the 3 and 4 position of the benzene ring. Several notable recreational drugs, such as
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...
(ecstasy),
methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamp ...
, and
cathinone
Cathinone (also known as benzoylethanamine, or β-keto-amphetamine) is a monoamine alkaloid found in the shrub ''Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the mai ...
s, are also members of the class. All of the
substituted amphetamine
Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with s ...
s are phenethylamines, as well.
Pharmaceutical drugs that are substituted phenethylamines include
phenelzine,
phenformin, and
fanetizole
Fanetizole is a drug that has immunoregulating activity.
Synthesis
Reaction of β-phenethylamine with ammonium isothiocyanate gives the thiourea (2). Treatment of that product with phenacyl bromide
Phenacyl bromide is the organic compound wi ...
, among many others.
Synthesis
One method for preparing β-phenethylamine, set forth in J. C. Robinson and H. R. Snyder's ''Organic Syntheses'' (published 1955), involves the reduction of
benzyl cyanide with
hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-to ...
in liquid
ammonia
Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...
, in the presence of a
Raney-Nickel catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
, 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.
Phenethylamine can also be produced via the cathodic reduction of
benzyl cyanide in a divided cell.
Assembling phenethylamine structures for synthesis of compounds such as epinephrine, amphetamines, tyrosine, and dopamine by adding the beta-aminoethyl side chain to the
phenyl
In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...
ring is possible. This can be done via
Friedel-Crafts acylation with N-protected
acyl chloride
In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...
s when the arene is activated, or by
Heck reaction
The Heck reaction (also called the Mizoroki–Heck reaction) is the chemical reaction of an unsaturated halide (or triflate) with an alkene in the presence of a base and a palladium catalyst (or palladium nanomaterial-based catalyst) to form a s ...
of the phenyl with N-vinyl
oxazolone, followed by
hydrogenation
Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...
, or by cross-coupling with beta-amino
organozinc
Organozinc compounds in organic chemistry contain carbon (C) to zinc (Zn) chemical bonds. Organozinc chemistry is the science of organozinc compounds describing their physical properties, synthesis and reactions.The Chemistry of Organozinc Compou ...
reagents, or reacting a brominated arene with beta-aminoethyl
organolithium
In organometallic chemistry, organolithium reagents are chemical compounds that contain carbon–lithium (C–Li) bonds. These reagents are important in organic synthesis, and are frequently used to transfer the organic group or the lithium atom ...
reagents, or by
Suzuki cross-coupling
The Suzuki reaction is an organic reaction, classified as a cross-coupling reaction, where the coupling partners are a boronic acid and an organohalide and the catalyst is a palladium(0) complex. It was first published in 1979 by Akira Suzuki, a ...
.
Detection in body fluids
Reviews that cover
attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
(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
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
greatly increase urinary phenethylamine concentration.
An ADHD
biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
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 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
A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
Catechol can be either a free molecule or a su ...
neurons from -
phenylalanine
Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amin ...
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 deaminated in the gut as it is a selective substrate for MAO-B, which is not found in the gut. Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine, and
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...
, 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.
Skydiving
Parachuting, including also skydiving, is a method of transiting from a high point in the Atmosphere of Earth, atmosphere to the surface of Earth with the aid of gravity, involving the control of speed during the descent using a parachut ...
has also been shown to induce a marked increase in urinary phenethylamine concentrations.
Pharmacology
Pharmacodynamics
Phenethylamine, being similar to
amphetamine in its action at their common
biomolecular targets,
releases norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...
and
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
.
Phenethylamine also appears to induce acetylcholine release via a glutamate-mediated mechanism.
Phenethylamine has been shown to bind to
human trace amine-associated receptor 1
Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ...
(hTAAR1) as an
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...
.
β-PEA is also an odorant binding TAAR4 in mice thought to mediate predator avoidance.
Pharmacokinetics
By
oral route
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are in ...
, phenethylamine's
half-life
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...
is 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
Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the ''MAOA'' gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, ...
(),
monoamine oxidase B (),
the
semicarbazide-sensitive amine oxidase
Primary-amine oxidase, also known as semicarbazide-sensitive amine oxidase (SSAO), is an enzyme () with the systematic name ''primary-amine:oxygen oxidoreductase (deaminating)''. This enzyme catalyses the following chemical reaction
: RCH2NH2 + H ...
s (SSAOs)
AOC2
Amine oxidase, copper containing 2 (AOC2) is a protein that in humans is encoded by the ''AOC2'' gene. The protein is a copper-containing primary amine oxidase enzyme.
Function
Copper amine oxidases catalyze the oxidative conversion of amines ...
and
AOC3
Amine oxidase, copper containing 3 (AOC3), also known as vascular adhesion protein (VAP-1) and HPAO is an enzyme that in humans is encoded by the AOC3 gene on chromosome 17. This protein is a member of the semicarbazide-sensitive amine oxidase (S ...
,
flavin-containing monooxygenase 3 (FMO3),
and
aralkylamine N-acetyltransferase
Aralkylamine ''N''-acetyltransferase (AANAT) (), also known as arylalkylamine ''N''-acetyltransferase or serotonin ''N''-acetyltransferase (SNAT), is an enzyme that is involved in the day/night rhythmic production of melatonin, by modification ...
(AANAT).
, an
isomer
In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers.
Is ...
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
Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The firs ...
metabolism and subsequent
aldehyde dehydrogenase metabolism.
Phenylacetaldehyde
Phenylacetaldehyde is an organic compound used in the synthesis of fragrances and polymers. Phenylacetaldehyde is an aldehyde that consists of acetaldehyde bearing a phenyl substituent; the parent member of the phenylacetaldehyde class of compound ...
is the intermediate product which is produced by monoamine oxidase and then further metabolized into β-phenylacetic acid by aldehyde dehydrogenase.
When the initial phenylethylamine concentration in the brain is low, brain levels can be increased when taking a
monoamine oxidase inhibitor
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, esp ...
(MAOI), particularly a
MAO-B inhibitor, and by times when the initial concentration is high.
See also
*
Alexander Shulgin
Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American medicinal chemist, biochemist, organic chemist, pharmacologist, psychopharmacologist, and author. He is credited with introducing 3,4-methylenedioxymetha ...
*
''N''-Methylphenethylamine
*
Phycomin
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 ami ...
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PiHKAL
Notes
References
External links
Phenethylamine MS Spectrum
{{TAAR ligands, state=expanded
Phenethylamine alkaloids
Amphetamine
Biomolecules
Euphoriants
Norepinephrine-dopamine releasing agents
Stimulants
TAAR1 agonists
Trace amines
VMAT inhibitors