Chemistry:2,5-Dimethoxy-4-ethylamphetamine

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Short description: Psychedelic drug
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DOET
File:DOET structure.svg
File:DOET ball-and-stick structure.png
Clinical data
Other namesDOET; DOEt; DOE; HECATE; Hecate; DMEA; 4-Ethyl-2,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-ethylamphetamine; Dimethoxyethylamphetamine; Ethyldimethoxyamphetamine
Drug classSerotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen; Stimulant; Antidepressant; Psychic energizer; Cognitive enhancer
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
MetabolismOxidation of the 4-position ethyl group[1][6]
Onset of action1–3 hours[1][2][3][4]
Duration of action5–20 hours[3][5]
ExcretionUrine (10–40% unchanged within 24 hours)[1][2][3]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC13H21NO2
Molar mass223.316 g·mol−1
3D model (JSmol)
  (verify)

DOET, also known as 4-ethyl-2,5-dimethoxyamphetamine or as Hecate, is a psychedelic drug of the phenethylamine, amphetamine, and DOx families.[7][5][2][1] It is closely related to DOM and is a synthetic analogue of the naturally occurring phenethylamine psychedelic mescaline.[1][8] The drug is the derivative of DOM in which the methyl group at the 4 position has been replaced with a ethyl group.[5] It is taken orally.[5][2][3] DOET has a slow onset of 1 to 3 hours, a delayed peak of 3 to 5 hours, and a dose-dependent and potentially very long duration of 5 to 20 hours.[5][9][1][2]

Effects of DOET at low doses include mild euphoria, enhanced self-awareness, and talkativeness, among others.[1][2][3] Mild closed-eye visuals can also occur.[10][4] At higher doses, DOET produces psychedelic effects including heightened emotions, sensory enhancement, rich closed-eye visuals, and open-eye visuals, among others.[5][4] Physical effects include pupil dilation, increased heart rate, and increased blood pressure.[3][11][12] It acts as a selective agonist of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors.[13][14][15]

DOET was first discovered by Alexander Shulgin in the 1960s.[16] It was clinically studied at low and sub-hallucinogenic doses for potential use as a pharmaceutical drug acting as a "psychic energizer" by Dow Chemical Company in the 1960s.[16] However, its development was terminated after DOM emerged as a street drug and caused a small public health crisis in San Francisco in 1967.[16][17] Nonetheless, DOET's effects at low doses were extensively characterized in small clinical trials.[1][3][11][10][4] The psychedelic effects of DOET at higher doses were subsequently described by Shulgin in his book PiHKAL (Phenethylamines I Have Known and Loved) in 1991.[5]

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists DOET's dose as 2 to 6 mg orally and its duration as 14 to 20 hours.[5][7] In experience reports of DOET at doses of 1 to 7 mg orally in different individuals, 1 mg produced relaxation but no psychedelic effects; 2.5 mg produced both open- and closed-eye visuals; 4 mg produced mood-energizing effects but very little or no hallucinogenic effect; 6 mg produced sensory enhancement, rich closed-eye visuals, and no open-eye visual movement; and 7 mg produced strong feelings with themes of love, eroticism, and divinity, openness, not much visually, closed-eye visuals, and body load symptoms.[5] There was considerable variation between individuals in terms of subjective effects.[5] Shulgin has described both DOET and DOM as being effective antidepressants at lower doses and DOET as being a cognitive enhancer at modest doses.[18][5] DOET, also known as Hecate, is one of Shulgin's "ten classic ladies", a series of methylated DOM derivatives.[5][19]

In a 1968 clinical trial, DOET at an oral dose of 1.5 mg (as the hydrochloride salt) produced mild euphoria and enhanced self-awareness, but no hallucinogenic effects (in terms of perceptual distortions or hallucinations/open-eye visuals), marked behavioral changes, or intellectual impairment.[1][2][3][11][12] Other reported effects included feeling high, feelings of insight, feelings of pleasantness, body image awareness, impatience, slight difficulty concentrating, talkativeness, racing thoughts, mild closed-eye visuals, time dilation in some, feeling alert, and feeling "washed out" after the drug.[1][3][11][12] Some of the effects of DOET in the study resembled those of dextroamphetamine, including talkativeness, euphoria, and feeling alert.[3][11] The subjective effects began 1 to 1.5 hours after dosing, peaked around 3 to 4 hours after administration, and the duration was about 5 to 6 hours.[1][2][3] Pupil dilation was also observed, but there were no marked changes in heart rate or blood pressure.[3][11][12] There were also changes on cognitive tests of association and serial learning.[1][3][11][12] The effects of DOET were similar to those of low doses of DOM (2.7–3.3 mg) but DOET appeared to be more potent (with 2.0 mg DOM being indistinguishable from placebo).[3][11]

In a subsequent 1971 clinical trial, DOET hydrochloride at oral doses of 0.75 to 4 mg again produced pupil dilation (dose-dependent), mild euphoria, feelings of enhanced self-awareness, and many of the other effects observed in the previous trial.[1][2][10] Once again, there were no hallucinogenic effects, aside from closed-eye visuals in a minority of individuals, and there was no cognitive impairment.[1][2][10] New assessed and reported effects included feeling relaxed, feelings of unpleasantness in some, lightheadedness, reduced depressive feelings, and feeling anxious or restless.[2][10] The feelings of nervousness and restlessness occurred more at the higher doses.[2][10] DOET appeared to show a greater apparent separation between threshold and hallucinogenic doses than had been documented for other psychedelics.[10][20] Other psychedelics like LSD and DOM show a 2- to 3-fold separation, whereas DOET showed an at least 5-fold separation.[10][20] The lesser influence of DOET on perceptual processes than equivalent doses of DOM was in spite of the greater potency of DOET than DOM in producing subjective effects in general.[10][20]

A third and final 1974 clinical trial assessed oral doses of 1 to 4 mg (S)-(+)-DOET, 1 to 2 mg (R)-(−)-DOET, and 2 to 4 mg (RS)-(±)-DOET.[1][21][4] It was found that 1 mg (R)-(−)-DOET was equivalent to 4 mg (S)-(+)-DOET in producing psychoactive effects and hence that (R)-(−)-DOET was about 4 times as potent as (S)-(+)-DOET.[1][21][4] The onset was 1.5 to 3 hours, peak effects were at 4 to 5 hours, and the duration was 6 to 10 hours.[4] The subjective effects were similar to the earlier trials, but new reported effects included enhanced perception of all senses, difficult-to-describe cognitive alteration, relaxed well-being, and heightened emotions with rapid mood changes.[4] No hallucinogenic effects or visual distortions with eyes open occurred, but vivid imagery with eyes closed could be experienced at the higher doses.[4]

Based on the preceding clinical trials, DOET does not produce clear hallucinogenic effects, aside from closed-eye visuals, at doses of up to 4 mg orally.[1][10][4] However, Shulgin has stated that DOET is psychedelic at doses of 3 mg and above orally.[7]

In line with notions that DOET is a "psychic energizer" at lower doses, the related psychedelic DOPR has shown pro-motivational effects in rodents at sub-hallucinogenic doses[22][23] and the related drug Ariadne (4C-DOM) has reportedly shown pro-motivational effects in monkeys despite being non-hallucinogenic.[24] ASR-2001 (2CB-5PrO), a non-hallucinogenic analogue of the related psychedelic 2C-B, is under development for use as a stimulant-like medication for the treatment of psychiatric disorders.[25][26][27][28][29]

Interactions

Pharmacology

Pharmacodynamics

DOET activities
Target Affinity (Ki, nM)
5-HT1A 14–9,727
5-HT1B 2,801
5-HT1D 6,615
5-HT1E 3,552
5-HT1F ND
5-HT2A 12–100 (Ki)
0.34–31 (EC50)
88–112% (Emax)
5-HT2B 29–174 (Ki)
68–236 (EC50)
73–108% (Emax)
5-HT2C 101–108 (Ki)
0.57–17.0 (EC50)
82–102% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 >10,000
5-HT7 1,225
α1A 4,006–>10,000
α1B >10,000
α1D ND
α2A 1,277–>4,970
α2B 574
α2C 1,447
β1 5,723
β2 2,195
D1–D5 >10,000
H1–H4 >10,000
M1, M3, M4 ND
M2, M5 >10,000
TAAR1 >30,000 (EC50)
I1 >10,000
σ1 9,780
σ2 9,560
SERT >10,000 (Ki)
NET >10,000 (Ki)
DAT >10,000 (Ki)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [30][31][15][13][14][32][33][34][35]

DOET acts as a selective serotonin 5-HT2 receptor agonist, including of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors.[13][14][15][36] In one study, its affinities (Ki) were 12 nM for the serotonin 5-HT2A receptor, 108 nM for the serotonin 5-HT2C receptor (9-fold lower than for 5-HT2A), and 9,727 nM for the serotonin 5-HT1A receptor (811-fold lower than for 5-HT2A).[14] The drug's EC50 for activation of the serotonin 5-HT2A receptor was 1.7 to 8.1 nM depending on the intracellular signaling cascade, while its Emax was 99%.[14] At the serotonin 5-HT2B receptor, its EC50 was 68 nM (8- to 40-fold lower than for 5-HT2A) and its Emax was 73%.[14] DOET is a full agonist of the serotonin 5-HT2A receptor and a high-efficacy partial agonist of the serotonin 5-HT2B and 5-HT2C receptors.[14][15] The drug is a very weak or inactive agonist of the human trace amine-associated receptor 1 (TAAR1) and is inactive at the rhesus monkey TAAR1.[32][14] In contrast to many other amphetamines, but like other DOx drugs, DOET does not bind to the monoamine transporters.[14][15]

DOET produces the head-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents.[13][37] As with other psychedelics, DOET shows a biphasic or inverted U-shaped dose–response curve for production of the HTR.[13][37] The drug induces the HTR to a similar maximal extent as other related psychedelics like DOM and DOI.[13][37] DOET substitutes for the phenethylamine psychedelics mescaline and DOM, partially substitutes for the tryptamine psychedelic 5-MeO-DMT, and does not substitute for the psychostimulant dextroamphetamine in animal drug discrimination tests.[38][39][40][41] DOET produces hyperlocomotion in mice.[42][43][44] However, like other psychedelics, it shows a biphasic or inverted U-shaped dose–response curve, increasing locomotor activity at low to moderate doses and reducing it at high doses.[42][43][44] DOET produces serotonin receptor-dependent pressor and hyperthermic effects in rodents.[44]

Pharmacokinetics

In terms of effects in humans, the onset of lower doses of DOET and its individual enantiomers (0.75–4 mg) is 1 to 3 hours, peak effects occur after 3 to 5 hours, and the duration is 5 to 10 hours.[1][2][3][11][10][4] At higher doses of DOET (2 to 6 mg), the duration was reported to be 14 to 20 hours.[5][7] DOET, like other DOx drugs, has an unusually slow onset and long duration.[9] The drug crosses the blood–brain barrier in rodents.[13] DOET is metabolized by oxidation of the ethyl group at the 4 position in rodents.[1][6] It appears to be metabolized more quickly than DOM.[1] In humans, DOET is excreted 10 to 40% in urine unchanged within 24 hours.[1][2][3] The greatest excretion rate occurred between 3 and 6 hours.[1][3]

Chemistry

DOET, also known as 4-ethyl-2,5-dimethoxyamphetamine or as 4-ethyl-2,5-dimethoxy-α-methylphenethylamine, is a substituted phenethylamine and amphetamine and is a member of the DOx group of drugs.[7][5][2][1] It is structurally related to the naturally occurring phenethylamine psychedelic mescaline (3,4,5-trimethoxyphenethylamine).[1][8]

Synthesis

The chemical synthesis of DOET has been described.[5][7]

Analogues

Analogues of DOET include other DOx drugs such as DOM, DOPR, DOBU, DOAM, DOB, DOI, DOEF, and DOTFE, among others.[5][7][1] The α-desmethyl or phenethylamine analogue of DOET is 2C-E.[7][5] Ariadne is the α-ethyl or phenylisobutylamine analogue of DOM.[45][5]

History

DOET was discovered by Alexander Shulgin in the 1960s.[16] He assessed DOET after synthesizing DOM in 1963 and discovering DOM's psychedelic effects in 1964.[16][46][47][7] Shulgin found that DOET was a remarkable "psychic energizer" at low doses without producing psychedelic effects at these doses.[16] The effects that he experienced included positive mood, talkativeness, and disinhibition that lasted the whole day.[16] In contrast to Shulgin however, a friend and colleague of Shulgin's that he had try DOET a month later only experienced intense lethargy followed by profound depression after taking the drug.[16] Nonetheless, Shulgin's enthusiasm was not dissuaded, and he felt that the drug should be exploited.[16] Shulgin was working at Dow Chemical Company at the time, and he pitched DOET to the company.[16] They selected DOET as a promising compound and decided to move forward with clinical trials for potential use as a pharmaceutical drug.[16] Shulgin and the company filed a patent for DOET in 1966, which was published in 1970.[16][46][7][48] Dow Chemical Company tasked neuroscientist Solomon H. Snyder at Johns Hopkins University with clinically studying DOET.[16]

In 1967, DOM emerged as a street drug and LSD replacement with the name "STP" in San Francisco and caused a small public health crisis.[16][17] This occurred after LSD distributor Owsley Stanley learned of DOM from Shulgin and began distributing very-high-dose DOM tablets for free.[16][17] LSD had become illegal in California in 1966 and an alternative had been sought by Stanley.[16] The DOET tablets he distributed could have very long durations (up to 3–4 days) and resulted in intense experiences, worrying physical side effects, and hospitalizations.[16] DOM was first described in the media and scientific literature in 1967 as a result of the crisis.[16][49][3] The drug became illegal in the United States in 1968.[16] It is unclear why Shulgin told Stanley about DOM and risked his professional career as well as the DOET clinical development.[16][17] However, it might have been because Shulgin felt that DOM was a promising compound but was not being further pursued by Dow Chemical Company and would otherwise be forgotten.[16][17]

Dow Chemical Company terminated its clinical research program on DOET due to the DOM public health crisis.[16] DOET was subsequently first described in the scientific literature by Snyder and colleagues in 1968.[3] Snyder continued to be interested in DOET as a potential medicine, but it was never further developed.[3] Snyder conducted and published a series of three clinical trials of low-dose DOET between 1968 and 1974.[3][11][12][10][4] In these trials, he compared DOET with DOM, dextroamphetamine, and placebo.[3][11][10][4] As with Shulgin, he found DOET to produce amphetamine-like mild euphoria and talkativeness, among other effects, without producing significant hallucinogenic effects at the assessed doses.[3][11][10] Snyder also studied the individual enantiomers of DOET.[1][21][4] Shulgin first discussed DOET in publications in 1969 and 1970.[46][16][50][51] DOET became a Schedule I controlled substance in the United States in February 1973.[52]

Ariadne (4C-D, 4C-DOM, BL-3912, Dimoxamine), the α-ethyl or phenylisobutylamine analogue of DOM, was developed by Shulgin in the 1970s.[45][5] He found it to be psychoactive and to produce "the alert of a psychedelic, with none of the rest of the package".[5][45] This threshold psychoactivity without psychedelic effects was reminiscent of low doses of DOET.[5][45] However, in contrast to DOET and other DOx drugs like DOM, Ariadne remained completely non-hallucinogenic even at very high doses, showing a hard ceiling to its psychoactive effects and a lack of recreational potential.[5][45] Ariadne was patented and developed by Shulgin and Bristol Laboratories for potential use as an antidepressant and for a variety of other clinical indications in the 1970s.[7][45][5] (R)-Ariadne (BL-3912A) completed phase 2 clinical trials and showed promising initial clinical benefits.[45] However, further clinical development was halted for strategic economic reasons.[45] In 2023, Ariadne was found to exhibit reduced-efficacy partial agonism of the serotonin 5-HT2A receptor compared to DOM, and this was considered to account for its dramatically reduced hallucinogenic potential.[45]

Shulgin first synthesized 2C-E, the α-desmethyl or phenethylamine analogue of DOET, in 1977.[53][54] Shulgin first published reports describing the psychedelic effects of higher doses of DOET in PiHKAL in 1991.[5] Prior to this, no reports had clearly been published of hallucinogenic effects of DOET, although Snyder had observed some closed-eye visuals with low-dose DOET in his clinical trials.[1][3][11][4] Shulgin also described 2C-E as producing robust psychedelic effects in PiHKAL, though with much higher doses required than DOET.[5]

Society and culture

Names

DOET was originally named DOE by Alexander Shulgin.[5][7] However, he subsequently recalled that this was also an acronym for desoxyephedrine (methamphetamine).[5] As a result, he changed his name for the drug from DOE to DOET or DOEt.[5][7] Other names that Shulgin has given DOET have included HECATE or Hecate (after the Greek goddess) and DMEA (short for dimethoxyethylamphetamine).[5][7]

United Nations

Internationally, DOET is a Schedule I controlled drug; under the Convention on Psychotropic Substances, it is legal only for medical uses or scientific research.[55]

Australia

DOET is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).[56] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[56]

Canada

DOET is a controlled substance in Canada.[57]

United States

DOET is classified as a Schedule I substance in the United States.[52][55]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 "Psychotomimetic Drugs: Structure-Activity Relationships". Stimulants. Boston, MA: Springer US. 1978. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6. https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 "Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives". Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Wiley. 9 March 2012. pp. 156–192. doi:10.1002/9781118105955.ch10. ISBN 978-0-471-72760-6. 
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 3.23 "DOM (STP), a new hallucinogenic drug, and DOET: effects in normal subjects". Am J Psychiatry 125 (3): 113–120. September 1968. doi:10.1176/ajp.125.3.357. PMID 4385937. 
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 "Stereospecific actions of DOET (2,5-dimethoxy-4-ethylamphetamine) in man". Arch Gen Psychiatry 31 (1): 103–106. July 1974. doi:10.1001/archpsyc.1974.01760130079013. PMID 4599412. 
  5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 5.22 5.23 5.24 5.25 5.26 5.27 5.28 PiHKAL: A Chemical Love Story. United States: Transform Press. September 1991. pp. 978. ISBN 0-9630096-0-5. https://erowid.org/library/books_online/pihkal/pihkal066.shtml. 
  6. ↑ 6.0 6.1 "Metabolic study of 2,5-dimethoxy-4-ethylamphetamine (DOET) in rats". Proc West Pharmacol Soc 18: 362. 1975. PMID 1182040. 
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 "#56. DOET (2,5-Dimethoxy-4-ethylamphetamine)". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. 1. Berkeley: Transform Press. 2011. pp. 106–110. ISBN 978-0-9630096-3-0. https://archive.org/details/shulgin-index-vol-1/page/106/mode/1up?view=theater. 
  8. ↑ 8.0 8.1 "Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs". Front Psychiatry 8. 2017. doi:10.3389/fpsyt.2017.00152. PMID 28868040. "The next, even though less accidental, producer of NPS hallucinogens was Alexander T. Shulgin, who synthesized hundreds of novel hallucinogenic tryptamines and phenylethylamines in his home laboratory. He described the synthesis of these compounds and also their psychotomimetic effects experienced in self-experiments in detail in his books PIHKAL and TIHKAL (199, 200). He created several dimethoxy-substituted phenylethylamines, such as DOM, 2,5-dimethoxy-4-bromoamphetamine (DOB), 2,5-dimethoxy-4-iodoamphetamine (DOI), and 2,5-dimethoxy-4-ethylamphetamine (DOET), which all display strong hallucinogenic properties. These drugs usually have much longer durations of action (12–30 h) and are much more potent agonists at 5-HT2A-Rs (50- to 175-fold) compared to their related phenylethylamine derivative mescaline (duration of action: 4–8 h) (189, 199, 200).". 
  9. ↑ 9.0 9.1 Katherine R. Bonson (9 September 2005). "Hallucinogenic Drugs". Encyclopedia of Life Sciences. Wiley. pp. 294–307. doi:10.1002/9780470015902.a0000166.pub2. ISBN 978-0-470-01617-6. "In the mid-1960s, structure–activity relationship investigations led to the synthesis of a new phenethylamine hallucinogen, 2,5-dimethoxy-4-methylamphetamine (DOM). [...] A threshold dose of DOM ranges from 3 to 10 mg orally. An extensive family of DOM derivatives have been synthesised, including DOB (substituting bromine at the 4-position), DOI (substituting an iodine group at the 4-position), and DOET (substituting an ethyl group at the 4-position) (Shulgin and Shulgin, 1991a,1991b). These drugs have a long onset time (up to 2 h) and their effects can persist for 15–20 h. The unusually long duration is related to their chemical structure. The presence of an alpha-methyl group on the phenethylamine physically prevents enzymatic degradation of the drug, extending the time the drug acts in the body." 
  10. ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 10.13 "DOET (2,5-dimethoxy-4-ethylamphetamine), a new psychotropic drug. Effects of varying doses in man". Arch Gen Psychiatry 24 (1): 50–55. January 1971. doi:10.1001/archpsyc.1971.01750070052006. PMID 4923215. 
  11. ↑ 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 11.11 11.12 "A new psychotropic agent. Psychological and physiological effects of 2,5-dimethoxy-4-ethyl amphetamine (DOET) in man". Arch Gen Psychiatry 21 (1): 95–101. July 1969. doi:10.1001/archpsyc.1969.01740190097014. PMID 4389442. 
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 "Altered free associations: Some cognitive effects of DOET (2, 5-dimethoxy-4-ethylamphetamine)". Behavioral Science 15 (4): 297–303. 1970. doi:10.1002/bs.3830150402. 
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 "The 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effects". Mol Psychiatry. November 2025. doi:10.1038/s41380-025-03325-1. PMID 41193673. https://www.nature.com/articles/s41380-025-03325-1.pdf. 
  14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7 14.8 "Monoamine Receptor and Transporter Interaction Profiles of 4-Alkyl-Substituted 2,5-Dimethoxyamphetamines". The FASEB Journal 36 (S1). 2022. doi:10.1096/fasebj.2022.36.S1.R2691. ISSN 0892-6638. https://www.researchgate.net/publication/360369275. 
  15. ↑ 15.0 15.1 15.2 15.3 15.4 "Psychedelics and the human receptorome". PLOS ONE 5 (2). February 2010. doi:10.1371/journal.pone.0009019. PMID 20126400. Bibcode: 2010PLoSO...5.9019R. 
  16. ↑ 16.00 16.01 16.02 16.03 16.04 16.05 16.06 16.07 16.08 16.09 16.10 16.11 16.12 16.13 16.14 16.15 16.16 16.17 16.18 16.19 16.20 16.21 16.22 "Learning about STP: A Forgotten Psychedelic from the Summer of Love". History of Pharmacy and Pharmaceuticals 65 (1): 93–116. 1 October 2023. doi:10.3368/hopp.65.1.93. ISSN 2694-3034. https://hopp.uwpress.org/content/wphopp/65/1/93.full.pdf. Retrieved 26 January 2025. 
  17. ↑ 17.0 17.1 17.2 17.3 17.4 "The origin of 2,5-dimethoxy-4-methylamphetamine (DOM, STP)". Drug Test Anal 16 (12): 1496–1508. December 2024. doi:10.1002/dta.3667. PMID 38419183. https://shulginresearch.net/wp-content/uploads/2024/03/The-origin-of-25-dimethoxy-4-methylamphetamine-DOM-STP.-Trout.-Drug-Test.-Anal.-DOI-10.1002-dta.3667-2024.pdf. 
  18. ↑ "Hallucinogens, CNS Stimulants, And Cannabis". Chemical and Biological Aspects of Drug Dependence. CRC Press. 1972. pp. 163–176. doi:10.1201/9780429260629-16. ISBN 978-0-87819-011-9. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=8d86c9d6e58771ccef891e76483b86fceee153f8. 
  19. ↑ "Triple Goddess of the Night". British Neuroscience Association Bulletin 63: 28–30. https://isomerdesign.com/bitnest/external/BNAB/63.30. 
  20. ↑ 20.0 20.1 20.2 "Phenylakylamines with potential psychotherapeutic utility. 1. 2-Amino-1-(2,5-dimethoxy-4-methylphenyl)butane". J Med Chem 19 (12): 1400–1404. December 1976. doi:10.1021/jm00234a010. PMID 1003425. https://erowid.org/archive/rhodium/pdf/shulgin/shulgin.4c-dom.pdf. "Interestingly, DOM and DOET both produced subjective effects of mild euphoria and enhanced self-awareness; however, DOM demonstrated clear-cut psychotomimetic-hallucinogenic effects at twice the minimal detectable dose, while DOET exhibited none of these at five times the minimal dosage. Shulgin and co-workers had noted similar potential with low dosages of DOB14 and 3,4-methylenedioxyamphetamine.15". 
  21. ↑ 21.0 21.1 21.2 "Absolute configuration and psychotomimetic activity". NIDA Research Monograph (22): 8–15. 1978. PMID 101890. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=2ab674b010611df18c029a78f6d17e52dba5f82f. 
  22. ↑ "Low (micro)doses of 2,5-dimethoxy-4-propylamphetamine (DOPR) increase effortful motivation in low-performing mice". Neuropharmacology 268. February 2025. doi:10.1016/j.neuropharm.2025.110334. PMID 39900138. 
  23. ↑ "ACNP 61st Annual Meeting: Poster Abstracts P541 - P809: P572. 2,5-Dimethoxy-4-Propylamphetamine (DOPR) Increased Effortful Motivation in Mice". Neuropsychopharmacology 47 (Suppl 1): 371–520 (390–390). December 2022. doi:10.1038/s41386-022-01486-z. PMID 36456695. 
  24. ↑ Alexander T. Shulgin; Ann Shulgin (1991). "#8 ARIADNE; 4C-DOM; BL-3912; DIMOXAMINE; 1-(2,5- DIMETHOXY-4-METHYLPHENYL)-2-AMINOBUTANE; 2,5- DIMETHOXY-a-ETHYL-4-METHYLPHENETHYLAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. pp. 475–480. ISBN 978-0-9630096-0-9. OCLC 25627628. https://www.erowid.org/library/books_online/pihkal/pihkal008.shtml. "His company did many animal tests, one of which showed that it was not hallucinogenic (a cat whose tail erected dramatically with DOM did nothing with ARIADNE) and another that showed re-motivation (some old maze-running monkeys who had decided not to run any more mazes changed their minds with ARIADNE)." 
  25. ↑ "The Heirs to a Vault of Novel Psychedelics Take a Trip Into the Unknown". 2 November 2023. https://doubleblindmag.com/sasha-shulgin-legacy/. 
  26. ↑ "What Happens When You Inherit 500 Psychedelic Compounds?". 30 March 2025. https://doubleblindmag.com/what-happens-when-you-inherit-500-psychedelic-compounds/. 
  27. ↑ "Innovative Approaches in Psychedelics, AI, and Communication: A Multi-Domain Perspective". ACS Med Chem Lett 16 (4): 514–516. April 2025. doi:10.1021/acsmedchemlett.5c00114. PMID 40236531. 
  28. ↑ "Pioneering Psychedelics Scientist Alexander "Sasha" Shulgin's Legacy Lives On Via New Compounds And Research". 10 July 2023. https://www.benzinga.com/markets/cannabis/23/07/33171977/pioneering-psychedelics-scientist-alexander-sasha-shulgins-legacy-lives-on-via-new-compounds-and. 
  29. ↑ ; Nicholas V. Cozzi & Paul F. Daley et al."Asymmetric phenylalkylamines" WO patent 2024243599A1, published 28 November 2024, assigned to Alexander Shulgin Research Institute
  30. ↑ "PDSP Database" (in zu). https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=doet&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query. 
  31. ↑ "BindingDB BDBM81965 1-(4-ethyl-2,5-dimethoxyphenyl)propan-2-amine::CAS_62066::CHEMBL8224::DOET,(-)::NSC_62066". https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=81965. 
  32. ↑ 32.0 32.1 "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorganic & Medicinal Chemistry 19 (23): 7044–7048. December 2011. doi:10.1016/j.bmc.2011.10.007. PMID 22037049. 
  33. ↑ "In vitro characterization of new psychoactive substances at the μ-opioid, CB1, 5HT1A, and 5-HT2A receptors-On-target receptor potency and efficacy, and off-target effects". Forensic Science International 317. December 2020. doi:10.1016/j.forsciint.2020.110553. PMID 33160102. 
  34. ↑ "5-HT2A, 5-HT2B and 5-HT2C receptor ligands". Pharmacochemistry Library. 27. Elsevier. 1997. pp. 161–197. doi:10.1016/s0165-7208(97)80013-x. ISBN 978-0-444-82041-9. 
  35. ↑ "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nat Commun 14 (1). December 2023. doi:10.1038/s41467-023-44016-1. PMID 38102107. Bibcode: 2023NatCo..14.8221W. 
  36. ↑ "Central serotonin receptors as targets for drug research". J Med Chem 30 (1): 1–12. January 1987. doi:10.1021/jm00384a001. PMID 3543362. "Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites". 
  37. ↑ 37.0 37.1 37.2 "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology 167. May 2020. doi:10.1016/j.neuropharm.2019.107933. PMID 31917152. 
  38. ↑ "The effects of 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-ethylamphetamine (DOET), d-amphetamine, and cocaine in rats trained with mescaline as a discriminative stimulus". Psychopharmacologia 44 (1): 29–32. October 1975. doi:10.1007/BF00421179. PMID 1197576. 
  39. ↑ "The discriminative stimulus properties of 2,5-dimethoxy-4-methylamphetamine (DOM): differentiation from amphetamine". Psychopharmacology (Berl) 68 (3): 209–215. 1980. doi:10.1007/BF00428105. PMID 6771804. 
  40. ↑ "DOM and related 2,5-dimethoxy-4-alkylphenylisopropylamines: behavioral and serotonin receptor properties". Pharmacol Biochem Behav 14 (3): 287–292. March 1981. doi:10.1016/0091-3057(81)90392-0. PMID 7232455. 
  41. ↑ "A comparison of the behavioral effects of DOM homologs". Pharmacol Biochem Behav 16 (4): 557–559. April 1982. doi:10.1016/0091-3057(82)90414-2. PMID 7071089. 
  42. ↑ 42.0 42.1 "Effect of Hallucinogens on Unconditioned Behavior". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. 36. 2018. pp. 159–199. doi:10.1007/7854_2016_466. ISBN 978-3-662-55878-2. 
  43. ↑ 43.0 43.1 "Role of the 5-HT₂A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice". Neuropharmacology 70: 218–227. July 2013. doi:10.1016/j.neuropharm.2013.01.014. PMID 23376711. 
  44. ↑ 44.0 44.1 44.2 "Some pharmacological actions of 2,5-dimethoxy-4-ethylamphetamine (DOET) in rats and mice". J Pharm Pharmacol 27 (1): 18–22. January 1975. doi:10.1111/j.2042-7158.1975.tb09372.x. PMID 235610. 
  45. ↑ 45.0 45.1 45.2 45.3 45.4 45.5 45.6 45.7 45.8 "Pharmacological Mechanism of the Non-hallucinogenic 5-HT2A Agonist Ariadne and Analogs". ACS Chemical Neuroscience 14 (1): 119–135. January 2023. doi:10.1021/acschemneuro.2c00597. PMID 36521179. 
  46. ↑ 46.0 46.1 46.2 "Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model". Drug Test Anal 4 (7–8): 556–576. 2012. doi:10.1002/dta.1333. PMID 22517680. 
  47. ↑ "Alexander Theodore Shulgin (1925-2014)". 9 June 2014. https://www.opendemocracy.net/en/alexander-theodore-shulgin-19252014/. "[Shulgin's] attention was drawn to the 4-position after he conceived of and synthesized the compound DOM, which he bioassayed on January 4, 1964 and discovered to be surprisingly potent: it was psychoactive at the 1 mg dose." 
  48. ↑ "phenethylamines and their pharmacologically-acceptable salts". 1970. https://patents.google.com/patent/US3547999A/en. 
  49. ↑ "2,5-dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug". Science 158 (3801): 669–670. November 1967. doi:10.1126/science.158.3801.669. PMID 4860952. Bibcode: 1967Sci...158..669S. 
  50. ↑ "Psychotomimetic Agents Related to the Catecholamines". Journal of Psychedelic Drugs 2 (2): 14–19. 1969. doi:10.1080/02791072.1969.10524409. ISSN 0022-393X. 
  51. ↑ Alexander Shulgin (1970). "Chemistry and Structure-Activity Relationships of the Psychotomimetics". in D. H. Efron. Psychotomimetic Drugs. New York: Raven Press. pp. 21–41. https://www.erowid.org/library/books_online/psychotomimetic_drugs.pdf#page=23. 
  52. ↑ 52.0 52.1 "Basic Pharmacology and Effects". Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. 2003. pp. 67–137. ISBN 978-0-12-433951-4. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6. Retrieved 1 February 2025. 
  53. ↑ "2C-x and DOx hallucinogens: A systematic review". Annals of the "Dunarea de Jos" University of Galati Fascicle II Mathematics Physics Theoretical Mechanics 44 (1): 46–52. 12 November 2021. doi:10.35219/ann-ugal-math-phys-mec.2021.1.07. ISSN 2668-7151. https://www.gup.ugal.ro/ugaljournals/index.php/math/article/download/4925/4350. Retrieved 26 January 2025. 
  54. ↑ Alexander Shulgin (1980). Pharmacology Notes II (The Shulgin Lab Books). Lafayette, CA, USA: Erowid. p. 236. https://erowid.org/library/books_online/shulgin_labbooks/shulgin_pharmacology_notebook9_searchable.pdf. 
  55. ↑ 55.0 55.1 List of psychotropic substances under international control (Report). August 2003. http://www.incb.org/pdf/e/list/green.pdf. 
  56. ↑ 56.0 56.1 "Poisons Standard". Therapeutics Goods Administration. Australian Government. October 2015. https://www.comlaw.gov.au/Details/F2015L01534. 
  57. ↑ "Controlled Drugs and Substances Act". https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 



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