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| Trade names | Monase[1] |
| Other names | alpha-Ethyltryptamine; αET; AET; α-ET; Etryptamine; PAL-125;[2] 3-(2-Aminobutyl)indole; 3-Indolylbutylamine; U-17312E; U17312E; Ro 3-1932; NSC-63963; NSC-88061, Etryptamine (USANUS) |
| Routes of administration | Oral[1] |
| Drug class | Entactogen;Stimulant;Monoamine releasing agent;Serotonin receptor agonist;Monoamine oxidase inhibitor[1] |
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| Metabolism | Hydroxylation[4] |
| Metabolites | • 6-Hydroxy-αET (inactive)[1][4] |
| Onset of action | 0.5–1.5 hours[4] |
| Eliminationhalf-life | ~8 hours[4] |
| Duration of action | 6–8 hours (100–150 mg)[5][4] |
| Excretion | Urine (majority)[4] |
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| Chemical and physical data | |
| Formula | C12H16N2 |
| Molar mass | 188.274 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 222 to 223 °C (432 to 433 °F) |
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α-Ethyltryptamine (αET,AET), also known asetryptamine, is anentactogen andstimulantdrug of thetryptamine family.[1][5][6] It was originally developed and marketed as anantidepressant under the brand nameMonase byUpjohn in the 1960s before beingwithdrawn due totoxicity.[1][5][7]
Side effects of αET includefacial flushing,headache,gastrointestinal distress,insomnia,irritability,appetite loss, andsedation, among others.[4] A rareside effect of αET isagranulocytosis.[1][6][8] αET acts as areleasing agent of serotonin, norepinephrine, and dopamine, as a weakserotonin receptor agonist, and as a weakmonoamine oxidase inhibitor.[1][5][2] It may also produceserotonergic neurotoxicity.[1][5][9] αET is asubstituted tryptamine and is closely related toα-methyltryptamine (αMT) and otherα-alkylated tryptamines.[1][5]
αET was first described in 1947.[1][10] It was used as an antidepressant for about a year around 1961.[1] The drug started being usedrecreationally in the 1980s and several deaths have been reported.[1][5][11][4] αET is acontrolled substance in various countries, including theUnited States andUnited Kingdom.[1][11] There has been renewed interest in αET, for instance as an alternative toMDMA, with the development ofpsychedelics and entactogens asmedicines in the 2020s.[1][5]
αET was previously used medically as anantidepressant and "psychic energizer" to treat people withdepression.[1][5][4][6] It was used for this indication under the brand name Monase.[1][5][4][6]
αET was availablepharmaceutically as theacetatesalt under the brand name Monase in the form of 15 mgoraltablets.[12][1]
αET is reported to haveentactogen and weakpsychostimulant effects.[1][5][6]Euphoria,increased energy,openness, andempathy have been specifically reported.[5][1][6] Unlike αMT and othertryptamines, αET is not reported to havepsychedelic orhallucinogenic effects.[5][6] The drug is described as less stimulating and intense thanMDMA ("ecstasy") but as otherwise having entactogenic effects resembling those of MDMA.[5][1] The dose of αET usedrecreationally has been reported to be 100 to 160 mg, itsonset of action has been reported to be 0.5 to 1.5 hours, and itsduration of action at the preceding doses is described as 6 to 8 hours.[1][5][4][6] Rapidtolerance to repeated administration of αET has been described.[6]
Side effects of αET at antidepressant doses have includedfacial flushing,headache,gastrointestinal distress,insomnia,irritability, andsedation.[4] Additional side effects of αET atrecreational doses have includedappetite loss and feelings ofintoxication.[4] Feelings oflethargy andsedation can occur once the drug wears off.[4]
As with many otherserotonin releasing agents,toxicity, such asserotonin syndrome, can occur whenexcessive doses are taken or when combined with certain drugs such asmonoamine oxidase inhibitors (MAOIs).[13] Several deaths have been associated with recreational use of αET.[1][11][4]
Rarely,agranulocytosis has occurred with prolonged administration of αET at antidepressant doses and has been said to have resulted in several cases and/or deaths.[1][4][8]
αET has been administered in clinical studies at doses of up to 300 mg per day.[1][4][14] An approximate but unconfirmed 700 mg dose resulted in fatalhyperthermia andagitateddelirium in one case.[1][4]LD50 doses of αET for various species have been studied and described.[1] Treatment of αETintoxication oroverdose is supportive.[4] Severe and potentially life-threateninghyperthermia may occur.[4]Serotonergic toxicity associated with serotonergic agents like αET can be managed withbenzodiazepines and with theserotonin receptor antagonistcyproheptadine.[15]
Similarly to αMT, αET is areleasing agent ofserotonin,norepinephrine anddopamine, withserotonin being the primaryneurotransmitter affected.[1][5][2] It is about 10-fold morepotent in inducing serotonin release than in inducing dopamine release and about 28-fold more potent in inducing serotonin release than in inducing norepinephrine release.[1][2] The (+)-enantiomer of αET, (+)-αET, is aserotonin–dopamine releasing agent (SDRA) and is one of the few such agents known.[2] 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.[2]
In addition to acting as amonoamine releasing agent, αET acts as aserotonin receptoragonist.[1] It is known to act as a weakpartial agonist of the serotonin5-HT2A receptor (EC50Tooltip half-maximal effective concentration > 10,000 nM;Emax = 21%).[1][5][2] (–)-αET is inactive as a 5-HT2A receptor agonist at concentrations of up to 10 μM, whereas (+)-αET is a 5-HT2A receptor agonist with an EC50 value of 1,250 nM and an Emax value of 61%.[2] αET has also been found to have weakaffinity for the5-HT1,5-HT1E,5-HT1F, and5-HT2B receptors.[1]
| Compound | Monoamine release (EC50Tooltip half-maximal effective concentration, nM) | 5-HT2A receptoragonism | |||
|---|---|---|---|---|---|
| Serotonin | Dopamine | Norepinephrine | EC50Tooltip half-maximal effective concentration (nM) | Emax (%) | |
| Tryptamine | 32.6 ± 2.6 | 164 ± 16 | 716 ± 46 | 7.36 ± 0.56 | 104 ± 4 |
| Serotonin | 44.4 ± 5.3 | >10,000 | >10,000 | ND | ND |
| N,N-DMT | 114 ± 15 | >10,000 | 4,166 ± 317 | 38.3 ± 0.81 | 83 ± 0.4 |
| αMT | 21.7 ± 1.0 | 78.6 ± 4.0 | 112 ± 6 | 23.1 ± 2.4 | 103 ± 3 |
| αET | 23.2 ± 1.7 | 232 ± 17 | 640 ± 76a | >10,000 | 21 ± 11 |
| (–)-αET | 54.9 ± 7.8 | 654 ± 50 | 3,670 ± 1,190a | >10,000 | – |
| (+)-αET | 34.7 ± 4.9 | 57.6 ± 3.1 | 592 ± 97a | 1,250 ± 310 | 61 ± 8 |
| MDMA | 56.6 ± 2.1 | 376 ± 16 | 77.4 ± 3.4 | ND | ND |
| Notes: The smaller the value, the more strongly the compound produces the effect.Footnotes:a = αET, (–)-αET, and (+)-αET were norepinephrine partial releasers withEmax values of 78%, 75%, and 71%, respectively.Refs:[1][2][16][17] | |||||
αET is a weakmonoamine oxidase inhibitor (MAOI).[1][18] It is specifically aselective andreversibleinhibitor ofmonoamine oxidase A (MAO-A).[1][18] AnIC50Tooltip half-maximal inhibitory concentration value of 260 μMin vitro and 80 to 100% inhibition of MAO-A at a dose of 10 mg/kg in ratsin vivo have been reported.[1][19] αET is described as slightly more potent as an MAOI thandextroamphetamine.[1] Both enantiomers of αET have similar activity as MAOIs, whereas αET's major metabolite 6-hydroxy-αET is inactive.[1] 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.[1][6]
The stimulant effects of αET have been said to lie primarily in (–)-αET, whereas hallucinogenic effects have been said to be present in (+)-αET.[1][4] However, these claims appear to be based on animal drug discrimination studies and are not necessarily in accordance with functional studies.[1][2] Generalization toDOMTooltip 2,5-dimethoxy-4-methylamphetamine may have been anomalous and due to the serotonin-releasing actions of αET rather than due to serotonin 5-HT2A receptor activation and associated psychedelic effects.[1] Accordingly, αET does not produce thehead-twitch response in rodents, unlike known psychedelics.[1] In addition, 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.[1]
αET has been found to produceserotonergic neurotoxicity similar to that of MDMA andpara-chloroamphetamine (PCA) in rats.[5][1][9] This has included long-lasting reductions inserotonin levels,5-hydroxyindoleacetic acid (5-HIAA) levels, and serotoninuptake sites in thefrontal cortex andhippocampus.[5][9] The dosage of αET employed was 8 doses of 30 mg/kg bysubcutaneous injection with doses spaced by 12-hour intervals.[5][9] There are prominent species differences in the neurotoxicity of monoamine releasing agents.[20][21] Primates appear to be more susceptible to the damage caused by serotonergic neurotoxins like MDMA than rodents.[20]
Theabsorption of αET appears to be rapid.[4] It has a relatively largevolume of distribution.[4] The drug undergoeshydroxylation to form the majormetabolite 6-hydroxy-αET (3-(2-aminobutyl)-6-hydroxyindole).[1][4] This metabolite is inactive.[4] αET iseliminated primarily inurine and a majority of a dose isexcreted in urine within 12 to 24 hours.[4] Itselimination half-life is approximately 8 hours.[4]
αET, also known as 3-(2-aminobutyl)indole, is asubstituted tryptamine andα-alkyltryptaminederivative.[1][5]Analogues of αET includeα-methyltryptamine (αMT) and other substituted α-alkylated tryptamines like5-MeO-αET,5-chloro-αMT (PAL-542), and5-fluoro-αET (PAL-545).[2]
αET was first described in thescientific literature in 1947.[1][10] Theenantiomers of αET were first individually described in 1970.[1]
Originally believed to exert its effects predominantly viamonoamine oxidase inhibition, αET wasdeveloped during the 1960s as anantidepressant byUpjohn chemical company in theUnited States under the generic name etryptamine and the brand name Monase, but was withdrawn from potential commercial use due to incidence ofidiosyncraticagranulocytosis in several patients.[1][6][8] It was on the market for about a year, around 1961, and was given to more than 5,000 patients, before being withdrawn.[1] αET was usually used as an antidepressant at doses of 30 to 40 mg/day (but up to 75 mg/day), which are lower than the doses that have been usedrecreationally.[1][5]
αET gained limited recreational popularity as adesigner drug with MDMA-like effects in the 1980s.[1] Subsequently, in theUnited States it was added to theSchedule I list ofillegal substances in 1993 or 1994.[1][6]
Etryptamine is the formalgeneric name of the drug and itsINNTooltip International Nonproprietary Name andBANTooltip British Approved Name.[22] In the case of theacetatesalt, its generic name isetryptamine acetate and this is itsUSANTooltip United States Adopted Name.[22] Etryptamine was usedpharmaceutically as etryptamine acetate.[22][1][12] Etryptamine is much more well known asalpha-ethyltryptamine orα-ethyltryptamine (abbreviated asαET,α-ET, orAET).[1][5][6] Other synonyms of αET and/or its acetate salt include3-(2-aminobutyl)indole,3-indolylbutylamine,PAL-125,U-17312E,Ro 3-1932,NSC-63963, andNSC-88061, as well as its former brand nameMonase.[22][23][24][2]
αET has been used as arecreational drug since the 1980s.[1][5][11][4] Purported street names include Trip, ET, Love Pearls, and Love Pills.[1][4]
αET is aSchedule Icontrolled substance in theUnited States and aClass A controlled substance in theUnited Kingdom.[1][11]
Besidesdepression, αET has been studied in people withschizophrenia and other conditions.[1]
This base, a-ET or etryptamine, was a promising anti-depressant, explored clinically as the acetate salt by Upjohn under the name of Monase. Its central stimulant activity is probably not due to its monoamineoxidase inhibition activity, but appears to stem from its structural relationship to the indolic psychedelics. It was withdrawn from potential commercial use with the appearance of an unacceptable incidence of a medical condition known as agranulocytosis, but the extra mural research into its action, among the lay population, goes on, [...]
MONASE--Upjohn Monase 15 mg. Monase, brand of etryptamine acetate is 3-(2-aminobutyl) indole acetate, developed in the Research Laboratories of the Upjohn Company. Each tablet contains etryptamine acetate 15 mg. Monase is indicated in a variety of psychiatric and medical conditions in which mental depression is prominent and for which mood elevation and psychomotor stimulation are considered beneficial. ADMINISTRATION AND DOSAGE: 30 mg. daily in divided doses. SUPPLIED: As coated, compressed tablets, 15 mg., in bottles of 100 and is a prescription product. The catalog number is 3522.
Drugs such as MDMA, ecstasy (3,4-methylenedioxymethamphetamine), if combined with MAOIs (including moclobemide) do also cause fatalities because they act as serotonin releasers
