ñ-Ethyltryptamine (ñET, AET), also known as etryptamine, is an entactogen and stimulant drug of the tryptamine family. It was originally developed and marketed as an antidepressant under the brand name Monase by Upjohn in the 1960s before being withdrawn due to toxicity.
Side effects of ñET include facial flushing, headache, gastrointestinal distress, insomnia, irritability, appetite loss, and sedation, among others. A rare side effect of ñET is agranulocytosis. ñET acts as a releasing agent of serotonin, norepinephrine, and dopamine, as a weak serotonin receptor agonist, and as a weak monoamine oxidase inhibitor. It may also produce serotonergic neurotoxicity. ñET is a substituted tryptamine and is closely related to ñ-methyltryptamine (ñMT) and other ñ-alkylated tryptamines.
ñET 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. ñET is a controlled substance in various countries, including the United States and United Kingdom. There has been renewed interest in ñET, for instance as an alternative to MDMA, with the development of psychedelics and entactogens as medicines in the 2020s.
ñET was previously used medically as an antidepressant and "psychic energizer" to treat people with depression. It was used for this indication under the brand name Monase. The drug was available pharmaceutically as the acetate salt under the brand name Monase as 15mg oral tablets.
ñET is reported to have entactogen and weak psychostimulant effects. Euphoria, increased energy, openness, and empathy have been specifically reported. Unlike ñMT and other tryptamines, ñET is not reported to have psychedelic or hallucinogenic effects. The drug is described as less stimulating and intense than MDMA ("ecstasy") but as otherwise having entactogenic effects resembling those of MDMA. The dose of ñET used recreationally has been reported to be 100 to 160mg, its onset of action has been reported to be 0.5 to 1.5hours, and its duration of action at the preceding doses is described as 6 to 8hours. Rapid tolerance to repeated administration of ñET has been described.
Side effects of ñET at antidepressant doses have included facial flushing, headache, gastrointestinal distress, insomnia, irritability, and sedation. Additional side effects of ñET at recreational doses have included appetite loss and feelings of intoxication. Feelings of lethargy and sedation can occur once the drug wears off.
As with many other serotonin releasing agents, toxicity, such as serotonin syndrome, can occur when excessive doses are taken or when combined with certain drugs such as monoamine oxidase inhibitors (MAOIs). Several deaths have been associated with recreational use of ñET.
Rarely, agranulocytosis has occurred with prolonged administration of ñET at antidepressant doses and has been said to have resulted in several cases and/or deaths.
ñET has been administered in clinical studies at doses of up to 300mg per day. An approximate but unconfirmed 700mg dose resulted in fatal hyperthermia and agitated delirium in one case. LD<sub>50</sub> doses of ñET for various species have been studied and described. Treatment of ñET intoxication or overdose is supportive. Severe and potentially life-threatening hyperthermia may occur. Serotonergic toxicity associated with serotonergic agents like ñET can be managed with benzodiazepines and with the serotonin receptor antagonist cyproheptadine.
Similarly to ñMT, ñET is a releasing agent of serotonin, norepinephrine and dopamine, with serotonin being the primary neurotransmitter 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 of ñET, (+)-ñET, is a serotoninâÂÂdopamine 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, ñET acts as a serotonin receptor agonist. It is known to act as a weak partial agonist of the serotonin 5-HT<sub>2A</sub> receptor ( > 10,000nM; E<sub>max</sub> = 21%). (âÂÂ)-ñET is inactive as a 5-HT<sub>2A</sub> receptor agonist at concentrations of up to 10üM, whereas (+)-ñET is a 5-HT<sub>2A</sub> receptor agonist with an EC<sub>50</sub> value of 1,250nM and an E<sub>max</sub> value of 61%. ñET has also been found to have weak affinity for the 5-HT<sub>1</sub>, 5-HT<sub>1E</sub>, 5-HT<sub>1F</sub>, and 5-HT<sub>2B</sub> receptors.
ñET is a weak monoamine oxidase inhibitor (MAOI). It is specifically a selective and reversible inhibitor of monoamine oxidase A (MAO-A). An value of 260üM in vitro and 80 to 100% inhibition of MAO-A at a dose of 10mg/kg in rats in vivo have been reported. ñET is described as slightly more potent as an MAOI than dextroamphetamine. Both enantiomers of ñET have similar activity as MAOIs, whereas ñET's major metabolite 6-hydroxy-ñET is inactive. The relatively weak MAOI actions of ñET have been considered unlikely to be involved in its stimulant, antidepressant, and other psychoactive effects by certain sources.
The stimulant effects of ñET have been said to lie primarily in (âÂÂ)-ñET, whereas hallucinogenic effects have been said to be present in (+)-ñET. 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 ñET rather than due to serotonin 5-HT<sub>2A</sub> receptor activation and associated psychedelic effects. Accordingly, ñET does not produce the head-twitch response in rodents, unlike known psychedelics. However, in another study, low doses of ñET (0.5âÂÂ1.0mg/kg) did not produce the head-twitch response but a high dose (5mg/kg) did produce the response. Clear hallucinogenic effects of ñET have never been documented in humans even at high doses, although the individual enantiomers of ñET have never been studied in humans.
ñET 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 serotonin levels, 5-hydroxyindoleacetic acid (5-HIAA) levels, and serotonin uptake sites in the frontal cortex and hippocampus. The dosage of ñET employed was 8doses of 30mg/kg by subcutaneous injection 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.
The absorption of ñET appears to be rapid. It has a relatively large volume of distribution. The drug undergoes hydroxylation to form the major metabolite 6-hydroxy-ñET (3-(2-aminobutyl)-6-hydroxyindole). This metabolite is inactive. ñET is eliminated primarily in urine and a majority of a dose is excreted in urine within 12 to 24hours. Its elimination half-life is approximately 8hours.
ñET, also known as ñ-ethyltryptamine or as 3-(2-aminobutyl)indole, is a substituted tryptamine and ñ-alkyltryptamine derivative.
The chemical synthesis of ñET has been described. It can be synthesised in a two-step synthesis with commercial chemicals via the Henry reaction aka Nitroadol condensation reaction between indole-3-carboxaldehyde and nitropropane under amine salt or ionic liquid catalysis which produces 3-(2-nitrobut-1-enyl)-1H-indole, 3-(2-nitrobut-1-enyl)-1H-indole can subsequently be reduced via a reducing like lithium aluminum hydride. to form ñ-ethyltryptamine.
Analogues of ñET include ñ-methyltryptamine (ñMT), ñ-propyltryptamine (ñPT), and other substituted ñ-alkylated tryptamines like 4-HO-ñET, 5-MeO-ñET, 5-chloro-ñMT (PAL-542), and 5-fluoro-ñET (PAL-545).
ñET was first described in the scientific literature in 1947. The enantiomers of ñET were first individually described in 1970.
Originally believed to exert its effects predominantly via monoamine oxidase inhibition, ñET was developed during the 1960s as an antidepressant by Upjohn chemical company in the United States under the generic name etryptamine and the brand name Monase, but was withdrawn from potential commercial use due to incidence of idiosyncratic agranulocytosis 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. ñET 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.
ñET gained limited recreational popularity as a designer drug with MDMA-like effects in the 1980s. Subsequently, in the United States it was added to the Schedule I list of illegal substances in 1993 or 1994.
Etryptamine is the formal generic name of the drug and its and . In the case of the acetate salt, 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 ñ-ethyltryptamine (abbreviated as ñET, ñ-ET, or AET). Other synonyms of ñET 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.
ñET has been used as a recreational drug since the 1980s. Purported street names include Trip, ET, Love Pearls, and Love Pills.
ñET (etryptamine) is a Schedule III controlled substance in Canada.
ñET is a Class A controlled substance in the United Kingdom.
ñET is a Schedule I controlled substance in the United States.
Besides depression, ñET has been studied in people with schizophrenia and other conditions.