Chemistry:2,5-Dimethoxy-4-ethoxyamphetamine

From HandWiki

MEM, also known as 2,5-dimethoxy-4-ethoxyamphetamine or as TMA2-4-EtO, is a psychedelic drug of the phenethylamine, amphetamine, and DOx families related to TMA-2.[1] It is the analogue of TMA-2 in which the methoxy group at the 4 position has been replaced with an ethoxy group.[1] The drug was first described in the scientific literature by Alexander Shulgin by 1968.[2]

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists MEM's dose as 20 to 50 mg orally and its duration as 10 to 14 hours.[1][3] Its effects have been reported to include color enhancement, visual phenomena, and pattern movement, among others.[1]

Interactions

Pharmacology

Pharmacodynamics

MEM activities
Target Affinity (Ki, nM)
5-HT1A >10,000
5-HT1B >10,000
5-HT1D >10,000
5-HT1E >10,000
5-HT1F ND
5-HT2A 73.0–3,948 (Ki)
47.5–295 (EC50)
88–105% (Emax)
5-HT2B 64.5–763 (Ki)
437–557 (EC50)
70–96% (Emax)
5-HT2C 124–>10,000 (Ki)
29.9–248 (EC50)
98–129% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 >10,000
5-HT7 7,156
α1A, α1B >10,000
α1D ND
α2A–α2C >10,000
β1, β2 >10,000
β3 ND
D1–D5 >10,000
H1–H4 >10,000
M1–M5 >10,000
I1 >10,000
σ1 5,077
σ2 >10,000
TAAR1 ND
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: [4][5][6][7][8][9][10]

MEM is a serotonergic psychedelic and acts as a selective serotonin 5-HT2 receptor agonist.[6][7][8][9][10] It is specifically a full agonist of the serotonin 5-HT2A and 5-HT2C receptors and to a lesser extent is a partial to full agonist of the serotonin 5-HT2B receptor.[6][7][9] The psychedelic effects of MEM are thought to be mediated by serotonin 5-HT2A receptor activation.[7]

Chemistry

MEM, also known as 2,5-dimethoxy-4-ethoxyamphetamine, is a phenethylamine, amphetamine, and DOx derivative. It is the analogue and derivative of 2,4,5-trimethoxyamphetamine (TMA-2) in which a 4-ethoxy group is present instead of a 4-methoxy group.

Synthesis

The chemical synthesis of MEM has been described.[1]

Derivatives

A variety of derivatives of MEM have been developed and studied, not only by Alexander Shulgin but also by for instance Daniel Trachsel and colleagues.[11][12] These include MPM, MIPM, MALM, MBM, MAM, MMALM, MFEM, MDFEM, and MTFEM, among others.[11][12][13]

History

MEM was first synthesized by Alexander Shulgin.[1][2] It was first described by him in the scientific literature by 1968.[2] Subsequently, Shulgin described MEM in greater detail in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1]

Society and culture

Canada

MEM is a controlled substance in Canada.[14]

United States

MEM is not an explicitly controlled substance in the United States.[15] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

See also

  • DOx (psychedelics)
  • TWEETIO § DOx compounds
  • EMM and MME

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Pihkal: A Chemical Love Story. Transform Press. 1991. ISBN 0-9630096-0-5. 
  2. ↑ 2.0 2.1 2.2 "The ethyl homologs of 2,4,5-trimethoxyphenylisopropylamine". J Med Chem 11 (1): 186–187. January 1968. doi:10.1021/jm00307a056. PMID 5637180. 
  3. ↑ "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. PMC 9191653. http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf. "Table 4 Human potency data for selected hallucinogens. [...]". 
  4. ↑ "Kᵢ Database". 28 March 2025. https://pdsp.unc.edu/kidb2/kidb/web/kis-results/index?KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=12946&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=12965&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D=. 
  5. ↑ Liu, Tiqing. "BindingDB BDBM50005255 (+/-)2-(4-Ethoxy-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::2-(4-Ethoxy-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::CHEMBL8225". https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50005255. 
  6. ↑ 6.0 6.1 6.2 "Psychedelics and the human receptorome". PLOS ONE 5 (2). February 2010. doi:10.1371/journal.pone.0009019. PMID 20126400. Bibcode: 2010PLoSO...5.9019R. 
  7. ↑ 7.0 7.1 7.2 7.3 "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. 
  8. ↑ 8.0 8.1 "Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors". Naunyn Schmiedebergs Arch Pharmacol 359 (1): 1–6. January 1999. doi:10.1007/pl00005315. PMID 9933142. 
  9. ↑ 9.0 9.1 9.2 "Binding and functional structure-activity similarities of 4-substituted 2,5-dimethoxyphenyl isopropylamine analogues at 5-HT2A and 5-HT2B serotonin receptors". Front Pharmacol 14. 2023. doi:10.3389/fphar.2023.1101290. PMID 36762110. 
  10. ↑ 10.0 10.1 "Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors". Drug Alcohol Depend 60 (2): 121–132. August 2000. doi:10.1016/s0376-8716(99)00148-9. PMID 10940539. 
  11. ↑ 11.0 11.1 "Receptor Interaction Profiles of 4-Alkoxy-Substituted 2,5-Dimethoxyphenethylamines and Related Amphetamines". Front Pharmacol 10. 2019. doi:10.3389/fphar.2019.01423. PMID 31849671. PMC 6893898. https://repositorium.meduniwien.ac.at/obvumwoa/content/titleinfo/5962415/full.pdf. 
  12. ↑ 12.0 12.1 "Fluorine in psychedelic phenethylamines". Drug Test Anal 4 (7–8): 577–590. 2012. doi:10.1002/dta.413. PMID 22374819. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=c7b41be36b1f580a264a752521d151e6e2d9409d. 
  13. ↑ "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. "3.3.5. 4-(n)-Propoxy-2,5-dimethoxyphenylisopropylamine An unpublished study of the 4-propoxy homolog of TMA-2 (63, 4-(n)-propoxy-2,5-dimethoxyphenylisopropylamine, MPM, 4-(n)-propoxy-2,5-dimethoxyamphetamine) indicates that it has threshold activity at an oral dose level of about 15 mg, as the hydrochloride. It is then approximately as effective, certainly not much less so, than the two lower homologs MEM (60) and TMA-2 (34). The two higher homologs, 4-(n)-butoxy-2,5-dimethoxyphenylisopropylamine and 4-(n)-amyloxy-2,5-dimethoxyphenylisopropylamine (MBM and MAM, respectively) were without any central effects at similar dosages (12 and 16 mg, respectively, orally, as the hydrochloride salts). Too little is known of this homologous series at the present time to generalize as to structure-activity relationships." 
  14. ↑ "Controlled Drugs and Substances Act". https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 
  15. ↑ Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026, https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:2,5-Dimethoxy-4-ethoxyamphetamine&oldid=4308377"