Α-Ethyltryptamine

Available forms

αET was available pharmaceutically as the acetate salt under the brand name Monase in the form of 15 mg oral tablets.^[12][1]

Pharmacodynamics

Similarly to αMT, αET is a releasing agent of serotonin, norepinephrine and dopamine, with serotonin being the primary neurotransmitter affected.^[1][5][2] 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.^[1][2] The (+)-enantiomer of αET, (+)-αET, is a serotonin–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 a monoamine releasing agent, αET acts as a serotonin receptor agonist.^[1] It is known to act as a weak partial agonist of the serotonin 5-HT_2A receptor (EC₅₀Tooltip half-maximal effective concentration > 10,000 nM; E_max = 21%).^[1][5][2] (–)-αET is inactive as a 5-HT_2A receptor agonist at concentrations of up to 10 μM, whereas (+)-αET is a 5-HT_2A receptor agonist with an EC₅₀ value of 1,250 nM and an E_max value of 61%.^[2] αET has also been found to have weak affinity for the 5-HT₁, 5-HT_1E, 5-HT_1F, and 5-HT_2B receptors.^[1]

αET is a weak monoamine oxidase inhibitor (MAOI).^[1][18] It is specifically a selective and reversible inhibitor of monoamine oxidase A (MAO-A).^[1][18] An IC₅₀Tooltip half-maximal inhibitory concentration value of 260 μM in vitro and 80 to 100% inhibition of MAO-A at a dose of 10 mg/kg in rats in vivo have been reported.^[1][19] αET is described as slightly more potent as an MAOI than dextroamphetamine.^[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 to DOMTooltip 2,5-dimethoxy-4-methylamphetamine 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.^[1] Accordingly, αET does not produce the head-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 produce serotonergic neurotoxicity similar to that of MDMA and para-chloroamphetamine (PCA) in rats.^[5][1][9] 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.^[5][9] The dosage of αET employed was 8 doses of 30 mg/kg by subcutaneous 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]

Pharmacokinetics

The absorption of αET appears to be rapid.^[4] It has a relatively large volume of distribution.^[4] The drug undergoes hydroxylation to form the major metabolite 6-hydroxy-αET (3-(2-aminobutyl)-6-hydroxyindole).^[1][4] This metabolite is inactive.^[4] αET is eliminated primarily in urine and a majority of a dose is excreted in urine within 12 to 24 hours.^[4] Its elimination half-life is approximately 8 hours.^[4]

Names

Etryptamine is the formal generic name of the drug and its INNTooltip International Nonproprietary Name and BANTooltip British Approved Name.^[22] In the case of the acetate salt, its generic name is etryptamine acetate and this is its USANTooltip United States Adopted Name.^[22] Etryptamine was used pharmaceutically as etryptamine acetate.^[22][1][12] Etryptamine is much more well-known as alpha-ethyltryptamine or α-ethyltryptamine (abbreviated as αET, α-ET, or AET).^[1][5][6] 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.^{[22][23][24][2]}

Recreational use

αET has been used as a recreational drug since the 1980s.^{[1][5][11][4]} Purported street names include Trip, ET, Love Pearls, and Love Pills.^[1][4]

Legal status

αET is a Schedule I controlled substance in the United States and a Class A controlled substance in the United Kingdom.^[1][11]