2,5-Dimethoxy-4-ethoxyamphetamine

Psychedelic drug verified verified 477211612 MEM MEM.svg skin-invert-image 250px MEM ball-and-stick structure.png bg-transparent 235px Oral Serotonin receptor agonist; Serotonin 5-HT2 receptor agonist; Serotonergic psychedelic; Hallucinogen None Schedule I Class B 10–14 hours correct CAS 16128-88-4 correct FDA 3I0ORO8174 542053 correct chemspider 472023 correct EBI 8225 2,5-Dimethoxy-4-ethoxyamphetamine; 4-Ethoxy-2,5-dimethoxyamphetamine; MEM; TMA2-4-EtO 1-[(4-ethoxy-2,5-dimethoxy)phenyl]propan-2-amine 13 21 1 3 O(c1cc(OC)c(cc1OC)CC(N)C)CC correct chemspider 1S/C13H21NO3/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 correct chemspider ITZLAXJQDMGDEO-UHFFFAOYSA-N 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. https://www.erowid.org/library/books_online/pihkal/pihkal122.shtml It is the analogue of TMA-2 in which the methoxy group at the 4 position has been replaced with an ethoxy group. The drug was first described in the scientific literature by Alexander Shulgin by 1968. Use and effects In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists MEM's dose as 20 to 50mg orally and its duration as 10 to 14hours. Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species Neuropharmacology 167 107933 May 2020 31917152 9191653 10.1016/j.neuropharm.2019.107933 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. [...] 2025-03-26 2025-03-26 https://web.archive.org/web/20250326111621/http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf dead Its onset is rapid at 10 to 30minutes and peak effects occur at about 1.5hours. The first noticeable decrease in effects occurred at 6hours and the decline is slow. The effects of MEM have been reported to include visual phenomena, color and contrast enhancement, introspection and fantasy, lucidity or clarity, insights, good feelings or pleasantness, euphoria, lots of energy, need to keep moving and hard to stay still, eroticism, and tactile sensitivity. It was described as being "intense yet serene". Other effects of MEM included physical discomfort, queasiness, tremors, bodily sensitivity, and difficulty sleeping. MEM has sometimes been combined with MDMA for the purpose of lessening MEM's physical side effects. Interactions Psychedelic drug#Interactions Trip killer#Serotonergic psychedelic antidotes 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 No data 5-HT2A 73.0–3,948 (Ki)47.5–295 (EC50 half-maximal effective concentration)88–105% (Emax maximal efficacy) 5-HT2B 64.5–763 (Ki)437–557 (EC50 half-maximal effective concentration)70–96% (Emax maximal efficacy) 5-HT2C 124–>10,000 (Ki)29.9–248 (EC50 half-maximal effective concentration)98–129% (Emax maximal efficacy) 5-HT3 >10,000 5-HT4 ND No data 5-HT5A >10,000 5-HT6 >10,000 5-HT7 7,156 α1A, α1B >10,000 α1D ND No data α2A–α2C >10,000 β1, β2 >10,000 β3 ND No data D1–D5 >10,000 H1–H4 >10,000 M1–M5 >10,000 I1 >10,000 σ1 5,077 σ2 >10,000 TAAR1 Trace amine-associated receptor 1 ND No data SERT Serotonin transporter >10,000 (Ki) NET Norepinephrine transporter >10,000 (Ki) DAT Dopamine transporter >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: Kᵢ Database PDSP 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= 28 March 2025Liu Tiqing BindingDB BDBM50005255 (+/-)2-(4-Ethoxy-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::2-(4-Ethoxy-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::CHEMBL8225 BindingDB https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50005255 28 March 2025 Ray TS Psychedelics and the human receptorome PLOS ONE 5 2 e9019 February 2010 20126400 2814854 10.1371/journal.pone.0009019 free 2010PLoSO...5.9019R Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar R, Halberstadt AL, McCorvy JD Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential Nat Commun 14 1 8221 December 2023 38102107 10724237 10.1038/s41467-023-44016-1 free 2023NatCo..14.8221W Nelson DL, Lucaites VL, Wainscott DB, Glennon RA 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 9933142 10.1007/pl00005315 Hemanth P, Nistala P, Nguyen VT, Eltit JM, Glennon RA, Dukat M 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 1101290 2023 36762110 9902381 10.3389/fphar.2023.1101290 free Glennon RA, Dukat M, Grella B, Hong S, Costantino L, Teitler M, Smith C, Egan C, Davis K, Mattson MV 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 10940539 10.1016/s0376-8716(99)00148-9 11380/17721 free MEM is a serotonergic psychedelic and acts as a selective serotonin 5-HT2 receptor agonist. 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. The psychedelic effects of MEM are thought to be mediated by serotonin 5-HT2A receptor activation. 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. 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. Kolaczynska KE, Luethi D, Trachsel D, Hoener MC, Liechti ME Receptor Interaction Profiles of 4-Alkoxy-Substituted 2,5-Dimethoxyphenethylamines and Related Amphetamines Front Pharmacol 10 1423 2019 31849671 6893898 10.3389/fphar.2019.01423 free https://repositorium.meduniwien.ac.at/obvumwoa/content/titleinfo/5962415/full.pdf Trachsel D Fluorine in psychedelic phenethylamines Drug Test Anal 4 7–8 577–590 2012 22374819 10.1002/dta.413 https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=c7b41be36b1f580a264a752521d151e6e2d9409d subscription These include MPM, MIPM, MALM, MBM, MAM, MMALM, MFEM, MDFEM, and MTFEM, among others. Shulgin AT Iversen LL, Iversen SD, Snyder SH Psychotomimetic Drugs: Structure-Activity Relationships Stimulants 243–333 1978 10.1007/978-1-4757-0510-2_6 Springer US Boston, MA 978-1-4757-0512-6 https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6 https://books.google.com/books?id=h0_uBwAAQBAJ&pg=PA261 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. History MEM was first synthesized by Alexander Shulgin. Shulgin AT The ethyl homologs of 2,4,5-trimethoxyphenylisopropylamine J Med Chem 11 1 186–187 January 1968 5637180 10.1021/jm00307a056 It was first described by him in the scientific literature by 1968. Subsequently, Shulgin described MEM in greater detail in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). Society and culture Legal status Canada MEM is a controlled substance in Canada.Controlled Drugs and Substances Act Department of Justice Canada https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html 19 January 2026 United States MEM is not an explicitly controlled substance in the United States. Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) January 2026 U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division United States https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf 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 External links MEM - Isomer Design MEM - PiHKAL - Erowid MEM - PiHKAL - Isomer Design The Small & Handy MEM Thread - Bluelight Category:5-HT2A agonists Category:5-HT2B agonists Category:5-HT2C agonists Category:DOx (psychedelics) Category:Ethoxy compounds Category:PiHKAL Category:Psychedelic phenethylamines