Aleph-2

Pharmaceutical compound
Aleph-2
Clinical data
Other namesALEPH-2; DOT-2; 4-Ethylthio-2,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-ethylthioamphetamine; 4-EtS-DMA
Routes of
administration		Oral[1][2]
Drug classSerotonergic psychedelic; Hallucinogen; Serotonin 5-HT2 receptor agonist
ATC code
  • None
Pharmacokinetic data
Duration of action8–16 hours[1][2]
Identifiers
  • 1-(4-ethylsulfanyl-2,5-dimethoxyphenyl)propan-2-amine
CAS Number
  • 185562-00-9
PubChem CID
  • 10264356
DrugBank
  • DB13940
ChemSpider
  • 8439835
UNII
  • Z1I419DRZZ
ChEMBL
  • ChEMBL339611
CompTox Dashboard (EPA)
  • DTXSID401043188
Chemical and physical data
FormulaC13H21NO2S
Molar mass255.38 g·mol−1
3D model (JSmol)
  • Interactive image
  • CCSC1=C(C=C(C(=C1)OC)CC(C)N)OC
  • InChI=1S/C13H21NO2S/c1-5-17-13-8-11(15-3)10(6-9(2)14)7-12(13)16-4/h7-9H,5-6,14H2,1-4H3
  • Key:MCYCODJKXUJSAT-UHFFFAOYSA-N

Aleph-2, or ALEPH-2, also known as 4-ethylthio-2,5-dimethoxyamphetamine, is a psychedelic drug of the phenethylamine, amphetamine, and DOx families.[1][2][3] It is one of the Aleph series of compounds.[1] The drug was encountered as a novel designer drug in Europe in 2023.[4]

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists Aleph-2's dose as 4 to 8 mg orally and its duration as 8 to 16 hours.[1][2] The effects of Aleph-2 have been reported to include "almost no visual phenomena" to "extraordinary visuals and interpretations", visual distortion and movement, enhanced auditory and tactile perception, and a sensation of physical warmth, and residual shakiness and muscle tremors, among others.[1][2] There is an unpredictability with the dosing and effects of Aleph-2, such that one person who took 4 mg had strong effects including ending up in a fetal position, in relative hibernation for several hours, and with substantial amnesia, whereas another person who took 8 mg experienced only a bare threshold including slight lightheadedness.[1]

Interactions

Pharmacology

Pharmacodynamics

Aleph-2 activities
Target Affinity (Ki, nM)
5-HT1A 1,674
5-HT1B 2,037
5-HT1D 1,532
5-HT1E 3,088
5-HT1F ND
5-HT2A 60.4 (Ki)
0.489–0.898 (EC50Tooltip half-maximal effective concentration)
104–108% (EmaxTooltip maximal efficacy)
5-HT2B 1.6
5-HT2C 50.3 (Ki)
0.0912–0.401 (EC50)
105–114% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 3,020
5-HT7 1,322
α1A >10,000
α1B >10,000
α1D ND
α2A 5,803
α2B 2,934
α2C 1,388
β1 6,792
β2 26.1
β3 ND
D1, D2 >10,000
D3 618.3
D4, D5 >10,000
H1–H4 >10,000
M1, M2 >10,000
M3 1,907
M4 >10,000
M5 8,018
I1 319.8
σ1 238.9
σ2 >10,000
TAAR1Tooltip Trace amine-associated receptor 1 ND
SERTTooltip Serotonin transporter 1,318 (Ki)
NETTooltip Norepinephrine transporter >10,000 (Ki)
DATTooltip Dopamine transporter >10,000 (Ki)
MAO-ATooltip Monoamine oxidase A 3,200–3,800 (IC50) (rat)
MAO-BTooltip Monoamine oxidase B >100,000 (IC50) (rat)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [5][6][3][7][8][9]

Aleph-2 acts as a serotonin 5-HT2 receptor agonist.[3][10] The drug is also a weak monoamine oxidase inhibitor (MAOI), with IC50Tooltip half-maximal inhibitory concentration values of 3,200 nM for monoamine oxidase A (MAO-A) and >100,000 nM for monoamine oxidase B (MAO-B).[7][8] Aleph-2 produces anxiolytic effects in rodents.[10][11][12]

Chemistry

Synthesis

The chemical synthesis of Aleph-2 has been described.[1][2]

Analogues

Analogues of Aleph-2 include Aleph, Aleph-4, Aleph-6, Aleph-7, and 2C-T-2, among others.[1][2]

History

Aleph-2 was first described in the scientific literature by Alexander Shulgin in 1978.[13][14][15][16] Subsequently, it was described in greater detail by Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1] Aleph-2 was encountered as a novel designer drug in Europe in 2023.[4]

Society and culture

United States

Aleph-2 is not a controlled substance in the United States as of 2011.[2]

See also

References

  1. ^ a b c d e f g h i j Shulgin T, Shulgin A (1991). "#4 ALEPH-2 2,5-DIMETHOXY-4-ETHYLTHIOAMPHETAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. pp. 464–467. ISBN 978-0-9630096-0-9. OCLC 25627628.
  2. ^ a b c d e f g h Shulgin A, Manning T, Daley PF (2011). "#4. ALEPH-2". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley, CA: Transform Press. p. 5. ISBN 978-0-9630096-3-0. OCLC 709667010.
  3. ^ a b c Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2) e9019. Bibcode:2010PLoSO...5.9019R. doi:10.1371/journal.pone.0009019. PMC 2814854. PMID 20126400.
  4. ^ a b "ALEPH-2". АИПСИН (in Russian). 1 May 1996. Retrieved 1 January 2026.
  5. ^ "Kᵢ Database". PDSP. 1 April 2025. Retrieved 1 April 2025.
  6. ^ Liu T. "BDBM50164337 2-(4-Ethylsulfanyl-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::CHEMBL339611". BindingDB. Retrieved 1 April 2025.
  7. ^ a b Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol. 10 1590. doi:10.3389/fphar.2019.01590. PMC 6989591. PMID 32038257.
  8. ^ a b Scorza MC, Carrau C, Silveira R, Zapata-Torres G, Cassels BK, Reyes-Parada M (December 1997). "Monoamine oxidase inhibitory properties of some methoxylated and alkylthio amphetamine derivatives: structure-activity relationships" (PDF). Biochem Pharmacol. 54 (12): 1361–1369. doi:10.1016/s0006-2952(97)00405-x. PMID 9393679.
  9. ^ Gallardo-Godoy A, Fierro A, McLean TH, Castillo M, Cassels BK, Reyes-Parada M, et al. (April 2005). "Sulfur-substituted alpha-alkyl phenethylamines as selective and reversible MAO-A inhibitors: biological activities, CoMFA analysis, and active site modeling". J Med Chem. 48 (7): 2407–2419. doi:10.1021/jm0493109. PMID 15801832.
  10. ^ a b Acuña-Castillo C, Scorza C, Reyes-Parada M, Cassels BK, Huidobro-Toro JP (November 2000). "ALEPH-2, a suspected anxiolytic and putative hallucinogenic phenylisopropylamine derivative, is a 5-HT2a and 5-HT2c receptor agonist". Life Sciences. 67 (26): 3241–3247. doi:10.1016/s0024-3205(00)00906-1. PMID 11191631.
  11. ^ Scorza MC, Reyes-Parada M, Silveira R, Viola H, Medina JH, Viana MB, et al. (June 1996). "Behavioral effects of the putative anxiolytic (+/-)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) in rats and mice". Pharmacology, Biochemistry, and Behavior. 54 (2): 355–361. doi:10.1016/0091-3057(95)02149-3. PMID 8743595.
  12. ^ Reyes-Parada M, Scorza C, Romero V, Silveira R, Medina JH, Andrus D, et al. (November 1996). "(+/-)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 354 (5): 579–585. doi:10.1007/BF00170831. PMID 8938655.
  13. ^ Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6.
  14. ^ Braun U, Braun G, Jacob P, Nichols DE, Shulgin AT (1978). "Mescaline Analogs: Substitutions at the 4-Position" (PDF). In Barnett G, Trsic M, Willette RE (eds.). QuaSAR: Quantitative Structure Activity Relationships Of Analgesics, Narcotic Antagonists, And Hallucinogens (PDF). National Institute on Drug Abuse Research Monograph Series. Vol. 22. National Institute on Drug Abuse. pp. 27–37. PMID 101882.
  15. ^ Shulgin AT (1980). "Hallucinogens". In Burger A, Wolf ME (eds.). Burger's Medicinal Chemistry. Vol. 3 (4 ed.). New York: Wiley. pp. 1109–1137. ISBN 978-0-471-01572-7. OCLC 219960627.
  16. ^ Shulgin AT (1982). "Chemistry of Psychotomimetics". In Hoffmeister F, Stille G (eds.). Psychotropic Agents, Part III: Alcohol and Psychotomimetics, Psychotropic Effects of Central Acting Drugs. Handbook of Experimental Pharmacology. Vol. 55. Berlin: Springer Berlin Heidelberg. pp. 3–29. doi:10.1007/978-3-642-67770-0_1. ISBN 978-3-642-67772-4. OCLC 8130916.
  • Aleph-2 - Isomer Design
  • Aleph-2 - PiHKAL - Erowid
  • Aleph-2 - PiHKAL - Isomer Design
  • Aleph-2 - The Shulgin Index
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