α-Ethyltryptamine (αET, AET), also known as etryptamine, is an

entactogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

and

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

of the

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

family. It was originally developed and marketed as an

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

under the brand name Monase by

Upjohn The Upjohn Company was an American pharmaceutical manufacturing firm (est. 1886) in Hastings, Michigan, by Dr. William E. Upjohn, an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friable ...

in the 1960s before being withdrawn due to

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of αET include facial flushing,

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, gastrointestinal distress,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

irritability Irritability is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimul ...

appetite loss Anorexia is a medical term for a loss of appetite. While the term outside of the scientific literature is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while o ...

, and

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

, among others. A rare

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

of αET is

agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing neutropenia in the circulating blood. I ...

. αET acts as a releasing agent of serotonin, norepinephrine, and dopamine, as a weak

serotonin receptor agonist A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin (5-hydroxytryptamine; 5-HT), a neurotransmitter and hormone and the endogenous ligand of t ...

, and as a weak

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, 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 antidepressa ...

. It may also produce serotonergic neurotoxicity. αET is a

substituted tryptamine Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine analogues), are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all trypt ...

and is closely related to α-methyltryptamine (αMT) and other α-alkylated tryptamines. αET was first described in 1947. It was used as an antidepressant for about a year around 1961. The drug started being used recreationally in the 1980s and several deaths have been reported. αET is a

controlled substance A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Sing ...

in various countries, including the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

and

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

. There has been renewed interest in αET, for instance as an alternative to

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

, with the development of psychedelics and entactogens as

medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...

s in the 2020s.

Medical uses

αET was previously used medically as an

and "psychic energizer" to treat people with depression. It was used for this indication under the brand name Monase.

Available forms

αET was available pharmaceutically as the

acetate An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic, or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

under the brand name Monase in the form of 15mg

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

tablets.

Effects

αET is reported to have

and weak

psychostimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...

effects.

Euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

, increased energy,

openness Openness is an overarching concept that is characterized by an emphasis on transparency and collaboration. That is, openness refers to "accessibility of knowledge, technology and other resources; the transparency of action; the permeability of or ...

, and

empathy Empathy is generally described as the ability to take on another person's perspective, to understand, feel, and possibly share and respond to their experience. There are more (sometimes conflicting) definitions of empathy that include but are ...

have been specifically reported. Unlike αMT and other

s, αET is not reported to have psychedelic or

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

ic effects. The drug is described as less stimulating and intense than

("ecstasy") but as otherwise having entactogenic effects resembling those of MDMA. The dose of αET used recreationally has been reported to be 100 to 160mg, its

onset of action Onset of action is the duration of time it takes for a drug's effects to come to prominence upon administration. With oral administration, it typically ranges anywhere from 20 minutes to over an hour, depending on the drug in question. Other meth ...

has been reported to be 0.5 to 1.5hours, and its

duration of action Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...

at the preceding doses is described as 6 to 8hours. Rapid tolerance to repeated administration of αET has been described.

Side effects

s of αET at antidepressant doses have included facial flushing,

, gastrointestinal distress,

, and

. Additional side effects of αET at recreational doses have included

and feelings of intoxication. Feelings of

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness, or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overw ...

and

can occur once the drug wears off. As with many other

serotonin releasing agent A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter ...

, such as

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

, can occur when excessive doses are taken or when combined with certain drugs such as

s (MAOIs). Several deaths have been associated with recreational use of αET. Rarely,

has occurred with prolonged administration of αET at antidepressant doses and has been said to have resulted in several cases and/or deaths.

Overdose

αET has been administered in clinical studies at doses of up to 300mg per day. An approximate but unconfirmed 700mg dose resulted in fatal

hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...

and agitated

delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...

in one case. LD₅₀ doses of αET for various species have been studied and described. Treatment of αET intoxication or

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

is supportive. Severe and potentially life-threatening

may occur. Serotonergic toxicity associated with serotonergic agents like αET can be managed with

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

s and with the

serotonin receptor antagonist A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin receptor, serotonin (5-HT) receptors. Types 5-HT2A antagonists Antagonists of the 5-HT2A, 5-HT2A re ...

cyproheptadine Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine, first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties. It was patented in 1959 a ...

Pharmacology

Pharmacodynamics

Similarly to αMT, αET is a releasing agent of

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

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. It is an amine synthesized ...

, with

being the primary

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

affected. It is about 10-fold more potent in inducing serotonin release than in inducing dopamine release and about 28-fold more potent in inducing serotonin release than in inducing norepinephrine release. The (+)-

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

of αET, (+)-αET, is a serotonin–dopamine releasing agent (SDRA) and is one of the few such agents known. It is about 1.7-fold more potent in inducing serotonin release than in inducing dopamine release, about 17-fold more potent in inducing serotonin release than in inducing norepinephrine release, and is about 10-fold more potent in inducing dopamine release than in inducing norepinephrine release. In addition to acting as a monoamine releasing agent, αET acts as a

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

. It is known to act as a weak

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

of the serotonin 5-HT_2A receptor ( > 10,000nM; E_max = 21%). (–)-αET is inactive as a 5-HT_2A receptor agonist at concentrations of up to 10μM, whereas (+)-αET is a 5-HT_2A receptor agonist with an EC₅₀ value of 1,250nM and an E_max value of 61%. αET has also been found to have weak

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the 5-HT₁, 5-HT_1E, 5-HT_1F, and 5-HT_2B receptors. αET is a weak

(MAOI). It is specifically a selective and reversible

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

monoamine oxidase A Monoamine oxidase A, also known as MAO-A, is an enzyme ( E.C. 1.4.3.4) 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 dea ...

(MAO-A). An value of 260μM ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' and 80 to 100% inhibition of MAO-A at a dose of 10mg/kg in rats ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

'' have been reported. αET is described as slightly more potent as an MAOI than

dextroamphetamine Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...

. Both enantiomers of αET have similar activity as MAOIs, whereas αET's major metabolite 6-hydroxy-αET is inactive. The relatively weak MAOI actions of αET have been considered unlikely to be involved in its stimulant, antidepressant, and other psychoactive effects by certain sources. The stimulant effects of αET have been said to lie primarily in (–)-αET, whereas hallucinogenic effects have been said to be present in (+)-αET. However, these claims appear to be based on animal drug discrimination studies and are not necessarily in accordance with functional studies. Generalization to may have been anomalous and due to the serotonin-releasing actions of αET rather than due to serotonin 5-HT_2A receptor activation and associated psychedelic effects. Accordingly, αET does not produce the

head-twitch response The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lys ...

in rodents, unlike known psychedelics. However, in another study, low doses of αET (0.5–1.0mg/kg) did not produce the head-twitch response but a high dose (5mg/kg) did produce the response. Clear hallucinogenic effects of αET have never been documented in humans even at high doses, although the individual enantiomers of αET have never been studied in humans. αET has been found to produce serotonergic neurotoxicity similar to that of MDMA and ''para''-chloroamphetamine (PCA) in rats. This has included long-lasting reductions in

levels, 5-hydroxyindoleacetic acid (5-HIAA) levels, and serotonin uptake sites in the

frontal cortex The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove betw ...

and

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

. The dosage of αET employed was 8doses of 30mg/kg by

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...

with doses spaced by 12-hour intervals. There are prominent species differences in the neurotoxicity of monoamine releasing agents. Primates appear to be more susceptible to the damage caused by serotonergic neurotoxins like MDMA than rodents.

Pharmacokinetics

The

absorption Absorption may refer to: Chemistry and biology *Absorption (biology), digestion **Absorption (small intestine) *Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials *Absorption (skin), a route by which su ...

of αET appears to be rapid. It has a relatively large

volume of distribution In pharmacology, the volume of distribution (VD, also known as apparent volume of distribution, literally, ''volume of dilution'') is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same c ...

. The drug undergoes

hydroxylation In chemistry, hydroxylation refers to the installation of a hydroxyl group () into an organic compound. Hydroxylations generate alcohols and phenols, which are very common functional groups. Hydroxylation confers some degree of water-solubility ...

to form the major

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

6-hydroxy-αET (3-(2-aminobutyl)-6-hydroxyindole). This metabolite is inactive. αET is eliminated primarily in

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

and a majority of a dose is excreted in urine within 12 to 24hours. Its

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

is approximately 8hours.

Chemistry

αET, also known as 3-(2-aminobutyl)indole, is a

and α-alkyltryptamine

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

. Analogues of αET include α-methyltryptamine (αMT) and other substituted α-alkylated tryptamines like 5-MeO-αET, 5-chloro-αMT (PAL-542), and 5-fluoro-αET (PAL-545).

History

αET was first described in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

in 1947. The

s of αET were first individually described in 1970. Originally believed to exert its effects predominantly via monoamine oxidase inhibition, αET was developed during the 1960s as an

by Upjohn chemical company in the

under the generic name etryptamine and the brand name Monase, but was withdrawn from potential commercial use due to incidence of

idiosyncratic An idiosyncrasy is a unique feature of something. The term is often used to express peculiarity. Etymology The term "idiosyncrasy" originates from Greek ', "a peculiar temperament, habit of body" (from ', "one's own", ', "with" and ', "blend ...

in several patients. It was on the market for about a year, around 1961, and was given to more than 5,000patients, before being withdrawn. αET was usually used as an antidepressant at doses of 30 to 40mg/day (but up to 75mg/day), which are lower than the doses that have been used recreationally. αET gained limited recreational popularity as a

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. ...

with MDMA-like effects in the 1980s. Subsequently, in the

it was added to the Schedule I list of illegal substances in 1993 or 1994.

Society and culture

Names

''Etryptamine'' is the formal generic name of the drug and its and . In the case of the

, its generic name is ''etryptamine acetate'' and this is its . Etryptamine was used pharmaceutically as etryptamine acetate. Etryptamine is much more well known as ''alpha-ethyltryptamine'' or ''α-ethyltryptamine'' (abbreviated as ''αET'', ''α-ET'', or ''AET''). Other synonyms of αET and/or its acetate salt include ''3-(2-aminobutyl)indole'', ''3-indolylbutylamine'', ''PAL-125'', ''U-17312E'', ''Ro 3-1932'', ''NSC-63963'', and ''NSC-88061'', as well as its former brand name ''Monase''.

Recreational use

αET has been used as a

recreational drug Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

since the 1980s. Purported street names include Trip, ET, Love Pearls, and Love Pills.

Legal status

αET is a Schedule I

in the

and a Class A controlled substance in the

Research

Besides depression, αET has been studied in people with

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

and other conditions.

References

External links

#11. α-ET - TiHKAL - Erowid

#11 α-ET - TiHKAL - isomer design

AET - Erowid
{{DEFAULTSORT:Ethyltryptamine, alpha- Alpha-Alkyltryptamines Antidepressants Designer drugs Entactogens Monoamine oxidase inhibitors Monoaminergic neurotoxins Non-hallucinogenic 5-HT2A receptor agonists Serotonin-norepinephrine-dopamine releasing agents Serotonin receptor agonists Stimulants Withdrawn drugs