DOx

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DOx drugs like DOM have been associated with certain side effects that have not occurred to the same extent with other psychedelics like LSD. Examples of such side effects include physical symptoms like sweating, tremors, and large increases in heart rate.

{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

The DOx drugs act as agonists of the serotonin 5-HT₂ receptors, including of the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors.{{cite journal | last1=Luethi | first1=Dino | last2=Rudin | first2=Deborah | last3=Hoener | first3=Marius C. | last4=Liechti | first4=Matthias E. | title=Monoamine Receptor and Transporter Interaction Profiles of 4-Alkyl-Substituted 2,5-Dimethoxyamphetamines | journal=The FASEB Journal | volume=36 | issue=S1 | date=2022 | issn=0892-6638 | doi=10.1096/fasebj.2022.36.S1.R2691 | page= | doi-access=free | url=https://www.researchgate.net/publication/360369275 }}{{cite journal | vauthors = Ray TS | title = Psychedelics and the human receptorome | journal = PLOS ONE | volume = 5 | issue = 2 | pages = e9019 | date = February 2010 | pmid = 20126400 | pmc = 2814854 | doi = 10.1371/journal.pone.0009019 | doi-access = free | bibcode = 2010PLoSO...5.9019R | url = }}{{cite book | vauthors = Wills B, Erickson T | chapter = Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives | editor-last=Barceloux | editor-first=Donald G. | title=Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants | publisher=Wiley | date=9 March 2012 | isbn=978-0-471-72760-6 | doi=10.1002/9781118105955.ch10 | pages=156–192 }}{{cite journal | vauthors = Pottie E, Cannaert A, Stove CP | title = In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor | journal = Arch Toxicol | volume = 94 | issue = 10 | pages = 3449–3460 | date = October 2020 | pmid = 32627074 | doi = 10.1007/s00204-020-02836-w | url = | hdl = 1854/LU-8687071 | hdl-access = free }} Their psychedelic effects are thought to be mediated specifically by activation of the serotonin 5-HT_2A receptor.{{cite book | last1=Nichols | first1 = D.E. | last2=Nichols | first2=C. D. | chapter=The Pharmacology of Psychedelics | editor1-last=Grob | editor1-first=C.S. | editor2-last=Grigsby | editor2-first=J. | title=Handbook of Medical Hallucinogens | publisher=Guilford Publications | year=2021 | isbn=978-1-4625-4544-5 | chapter-url=https://books.google.com/books?id=ebb2DwAAQBAJ&pg=PA3 | access-date=17 January 2025 | pages=3–28 | quote=Phenylalkylamine hallucinogens such as DOM, DOI, and DOB are highly selective for 5-HT2 receptor subtypes (Pierce & Peroutka, 1989; Titeler, Lyon, & Glennon, 1988), and there is a consensus in the literature that the behavioral effects of psychedelics are primarily mediated by the 5-HT2A receptor (Halberstadt, 2015; Nichols, 2016). }}{{cite journal | vauthors = Glennon RA, Dukat M | title = 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review | journal = ACS Pharmacol Transl Sci | volume = 7 | issue = 6 | pages = 1722–1745 | date = June 2024 | pmid = 38898956 | doi = 10.1021/acsptsci.4c00157 | pmc = 11184610 | pmc-embargo-date = May 8, 2025 | url = }}

In contrast to other amphetamines, DOx drugs like DOC, DOET, and DOM are inactive as monoamine releasing agents and reuptake inhibitors.{{cite journal | vauthors = Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB | title = Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function | journal = Psychopharmacology (Berl) | volume = 231 | issue = 5 | pages = 875–888 | date = March 2014 | pmid = 24142203 | pmc = 3945162 | doi = 10.1007/s00213-013-3303-6 | url = }}{{cite journal | vauthors = Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A | title = Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors | journal = Biochem Pharmacol | volume = 158 | issue = | pages = 27–34 | date = December 2018 | pmid = 30261175 | pmc = 6298744 | doi = 10.1016/j.bcp.2018.09.024 | url = }} Some of the DOx drugs, including DOB, DOET, DOI, and DOM, are agonists of the rat, rhesus monkey, and/or human trace amine-associated receptor 1 (TAAR1) with varying potencies.{{cite journal | vauthors = Lewin AH, Miller GM, Gilmour B | title = Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | journal = Bioorg Med Chem | volume = 19 | issue = 23 | pages = 7044–7048 | date = December 2011 | pmid = 22037049 | pmc = 3236098 | doi = 10.1016/j.bmc.2011.10.007 | url = }}{{cite journal | vauthors = Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK | title = Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor | journal = Mol Pharmacol | volume = 60 | issue = 6 | pages = 1181–1188 | date = December 2001 | pmid = 11723224 | doi = 10.1124/mol.60.6.1181 | url = }}

In contrast to amphetamines like (–)-cathinone, but similarly to mescaline, DOM has shown no stimulant-like or reinforcing effects in rhesus monkeys.{{cite journal | vauthors = Fantegrossi WE, Murnane KS, Reissig CJ | title = The behavioral pharmacology of hallucinogens | journal = Biochem Pharmacol | volume = 75 | issue = 1 | pages = 17–33 | date = January 2008 | pmid = 17977517 | pmc = 2247373 | doi = 10.1016/j.bcp.2007.07.018 | url = | quote = Despite the reasonably constant recreational use of hallucinogens since at least the early 1970s [44], the reinforcing effects of hallucinogens have not been widely investigated in laboratory animals. Indeed, one of the earliest studies on the reinforcing effects of drugs using the intravenous self-administration procedure in rhesus monkeys found that no animal initiated self-injection of mescaline either spontaneously or after one month of programmed administration [45]. Likewise, the phenethylamine hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) was not effective in maintaining self-administration in rhesus monkeys [46]. Nevertheless, the hallucinogen-like phenethylamine 3,4-methylenedioxymethamphetamine (MDMA) has been shown to act as a reinforcer in intravenous self-administration paradigms in baboons [47], rhesus monkeys [48 – 50], rats [51] and mice [52]. }}{{cite journal | vauthors = Canal CE, Murnane KS | title = The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens | journal = J Psychopharmacol | volume = 31 | issue = 1 | pages = 127–143 | date = January 2017 | pmid = 27903793 | doi = 10.1177/0269881116677104 | url = | quote = One of the earliest studies on the reinforcing effects of drugs using the intravenous self-administration procedure in rhesus monkeys found that no animal initiated self-injection of mescaline either spontaneously or after one month of programmed administration, [...] (Deneau et al., 1969). The lack of mescaline self-administration stood in contrast to positive findings of self-administration of morphine, codeine, cocaine, amphetamine, pentobarbital, ethanol, and caffeine. A subsequent study with rhesus monkeys using 2,5-dimethoxy-4-methylamphetamine (DOM; Yanagita, 1986) provided similar results as the mescaline study. These findings have withstood the test of time, as the primary literature is virtually devoid of any accounts of self-administration of [classical hallucinogens (CH)], suggesting that there are very limited conditions under which laboratory animals voluntarily consume CH. | pmc = 5445387 }}{{cite journal | vauthors = Yanagita T | title = Intravenous self-administration of (-)-cathinone and 2-amino-1-(2,5-dimethoxy-4-methyl)phenylpropane in rhesus monkeys | journal = Drug Alcohol Depend | volume = 17 | issue = 2–3 | pages = 135–141 | date = June 1986 | pmid = 3743404| doi = 10.1016/0376-8716(86)90004-9 | url = }}{{cite journal | vauthors = Maguire DR | title = Evaluation of potential punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in rhesus monkeys responding under a choice procedure | journal = Behav Pharmacol | volume = 35 | issue = 7 | pages = 378–385 | date = October 2024 | pmid = 39052019 | doi = 10.1097/FBP.0000000000000787 | pmc = 11398979 | pmc-embargo-date = October 1, 2025 | url = }} Conversely however, DOC has shown reinforcing effects, including conditioned place preference (CPP) and self-administration, in rodents similarly to methamphetamine.{{cite journal | vauthors = Cha HJ, Jeon SY, Jang HJ, Shin J, Kim YH, Suh SK | title = Rewarding and reinforcing effects of 4-chloro-2,5-dimethoxyamphetamine and AH-7921 in rodents | journal = Neurosci Lett | volume = 676 | issue = | pages = 66–70 | date = May 2018 | pmid = 29626650 | doi = 10.1016/j.neulet.2018.04.009 | url = }} This is analogous to other findings in which various 2C and NBOMe drugs have been found to produce brain dopaminergic elevations and reinforcing effects in rodents.{{cite journal | vauthors = Gil-Martins E, Barbosa DJ, Borges F, Remião F, Silva R | title = Toxicodynamic insights of 2C and NBOMe drugs - Is there abuse potential? | journal = Toxicol Rep | volume = 14 | issue = | pages = 101890 | date = June 2025 | pmid = 39867514 | doi = 10.1016/j.toxrep.2025.101890 | url = | pmc = 11762925 | bibcode = 2025ToxR...1401890G }}{{cite journal | vauthors = Kim YJ, Ma SX, Hur KH, Lee Y, Ko YH, Lee BR, Kim SK, Sung SJ, Kim KM, Kim HC, Lee SY, Jang CG | title = New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents | journal = Arch Toxicol | volume = 95 | issue = 4 | pages = 1413–1429 | date = April 2021 | pmid = 33515270 | doi = 10.1007/s00204-021-02980-x | bibcode = 2021ArTox..95.1413K | url = }}{{cite journal | vauthors = Custodio RJ, Sayson LV, Botanas CJ, Abiero A, You KY, Kim M, Lee HJ, Yoo SY, Lee KW, Lee YS, Seo JW, Ryu IS, Kim HJ, Cheong JH | title = 25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential | journal = Addict Biol | volume = 25 | issue = 6 | pages = e12850 | date = November 2020 | pmid = 31749223 | doi = 10.1111/adb.12850 | url = }}{{cite journal | vauthors = Seo JY, Hur KH, Ko YH, Kim K, Lee BR, Kim YJ, Kim SK, Kim SE, Lee YS, Kim HC, Lee SY, Jang CG | title = A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents | journal = Brain Res Bull | volume = 152 | issue = | pages = 19–26 | date = October 2019 | pmid = 31279579 | doi = 10.1016/j.brainresbull.2019.07.002 | url = }}{{cite journal | vauthors = Jo C, Joo H, Youn DH, Kim JM, Hong YK, Lim NY, Kim KS, Park SJ, Choi SO | title = Rewarding and Reinforcing Effects of 25H-NBOMe in Rodents | journal = Brain Sci | volume = 12 | issue = 11 | date = November 2022 | page = 1490 | pmid = 36358416 | pmc = 9688077 | doi = 10.3390/brainsci12111490 | doi-access = free | url = }}{{cite journal | vauthors = Lee JG, Hur KH, Hwang SB, Lee S, Lee SY, Jang CG | title = Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System | journal = ACS Chem Neurosci | volume = 14 | issue = 15 | pages = 2658–2666 | date = August 2023 | pmid = 37463338 | doi = 10.1021/acschemneuro.3c00196 | url = }}{{cite journal | vauthors = Kim YJ, Kook WA, Ma SX, Lee BR, Ko YH, Kim SK, Lee Y, Lee JG, Lee S, Kim KM, Lee SY, Jang CG | title = The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents | journal = Arch Pharm Res | volume = 47 | issue = 4 | pages = 360–376 | date = April 2024 | pmid = 38551761 | doi = 10.1007/s12272-024-01491-4 | url = }}

The DOx drugs are orally active and many have doses in the range of 1 to 10{{nbsp}}mg and durations in the range of 8 to 30{{nbsp}}hours.{{cite journal | vauthors = Ballentine G, Friedman SF, Bzdok D | title = Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences | journal = Sci Adv | volume = 8 | issue = 11 | pages = eabl6989 | date = March 2022 | pmid = 35294242 | pmc = 8926331 | doi = 10.1126/sciadv.abl6989 | bibcode = 2022SciA....8L6989B | url = }}{{cite journal | vauthors = Jacob P, Shulgin AT | title = Structure-activity relationships of the classic hallucinogens and their analogs | journal = NIDA Res Monogr | volume = 146 | issue = | pages = 74–91 | date = 1994 | pmid = 8742795 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 }} Some DOx drugs, such as DOM and DOB, appear to have durations that increase non-linearly with dosage, for instance 8{{nbsp}}hours at lower doses and as long as 30{{nbsp}}hours or even up to 3 or 4{{nbsp}}days at higher doses. This suggests that the pathways mediating the metabolism of these drugs can saturate. The DOx drugs are metabolized primarily by O-demethylation. However, DOM is primarily metabolized by hydroxylation at its methyl group.

DOM was the first psychedelic of the DOx series to be discovered.{{cite journal | vauthors = Canal CE, Morgan D | title = 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 | journal = Drug Test Anal | volume = 4 | issue = 7–8 | pages = 556–576 | date = 2012 | pmid = 22517680 | pmc = 3722587 | doi = 10.1002/dta.1333 | url = }} It was first synthesized by Alexander Shulgin at Dow Chemical Company in 1963, who had had his first psychedelic experience, with mescaline (3,4,5-trimethoxyphenethylamine), in 1960. Shulgin personally tried DOM on January 4, 1964 and discovered its psychedelic effects.{{cite web | title=Alexander Theodore Shulgin (1925-2014) | website=openDemocracy | date=9 June 2014 | url=https://www.opendemocracy.net/en/alexander-theodore-shulgin-19252014/ | access-date=26 January 2025 | quote=[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. }}{{cite journal | last=Baggott | first=Matthew J. | title=Learning about STP: A Forgotten Psychedelic from the Summer of Love | journal=History of Pharmacy and Pharmaceuticals | volume=65 | issue=1 | date=1 October 2023 | issn=2694-3034 | doi=10.3368/hopp.65.1.93 | doi-access=free | pages=93–116 | url=https://hopp.uwpress.org/content/wphopp/65/1/93.full.pdf | access-date=26 January 2025}} 2,4,5-Trimethoxyamphetamine (TMA-2; "DOMeO") had been synthesized by Bruckner in 1933, but its psychedelic effects were not described until Shulgin tried the compound and reported its effects in the scientific literature in 1964.{{cite journal | last=Bruckner | first=Viktor | title=Über das Pseudonitrosit des Asarons | journal=Journal für Praktische Chemie | volume=138 | issue=9–10 | date=24 October 1933 | issn=0021-8383 | doi=10.1002/prac.19331380907 | pages=268–274}}{{cite journal | vauthors = Shulgin AT | title = Psychotomimetic amphetamines: methoxy 3,4-dialkoxyamphetamines | journal = Experientia | volume = 20 | issue = 7 | pages = 366–367 | date = July 1964 | pmid = 5855670 | doi = 10.1007/BF02147960 | url = }} Prior to this, 3,4,5-trimethoxyamphetamine (TMA; α-methylmescaline) had been synthesized by Hey in 1947, being found by him to produce euphoria, and was described by Peretz and colleagues in 1955 as clearly producing psychedelic effects.{{cite journal | vauthors = Peretz DI, Smythies JR, Gibson WC | title = A new hallucinogen: 3,4,5-trimethoxyphenyl-beta-aminopropane with notes on the stroboscopic phenomenon | journal = J Ment Sci | volume = 101 | issue = 423 | pages = 317–329 | date = April 1955 | pmid = 13243046 | doi = 10.1192/bjp.101.423.317 | url = | quote = 3,4,5-Trimethoxyphenyl-β-aminopropane (Trimethoxyamphetamine, TMA) was first synthesized by Hey in 1947 (Hey, 1947) who was impressed with its euphoric properties (private communication). [...] }}{{cite journal | last1=Shulgin | first1=Alexander T. | last2=Bunnell | first2=Sterling | last3=Sargent | first3=Thornton | title=The Psychotomimetic Properties of 3,4,5-Trimethoxyamphetamine | journal=Nature | volume=189 | issue=4769 | date=1961 | issn=0028-0836 | doi=10.1038/1891011a0 | pages=1011–1012| bibcode=1961Natur.189.1011S }}{{cite journal | vauthors = Hey P | title = The synthesis of a new homologue of mescaline | journal = Q J Pharm Pharmacol | volume = 20 | issue = 2 | pages = 129–134 | date = 1947 | pmid = 20260568 | doi = | url = https://www.thevespiary.org/rhodium/Rhodium/chemistry/tma.hey.html | archive-url = https://web.archive.org/web/20190719130050/https://www.thevespiary.org/rhodium/Rhodium/chemistry/tma.hey.html | archive-date = 19 July 2019 }}

Following his discovery of DOM, Shulgin developed DOET and found that at low doses it was a remarkable "psychic energizer" without producing psychedelic effects at these doses. Dow Chemical Company decided to move forward with clinical trials of DOET as a potential pharmaceutical drug for such purposes. Shulgin and Dow Chemical Company filed a patent for DOET in 1966, although it was not published until 1970.{{cite web | title=phenethylamines and their pharmacologically-acceptable salts | website=Google Patents | date=1970 | url=https://patents.google.com/patent/US3547999A/en | access-date=26 January 2025}} Dow Chemical Company tasked Solomon H. Snyder at Johns Hopkins University with clinically studying DOET.

In April 1967, following the banning of LSD in California in 1966, DOM emerged as a street drug and legal LSD alternative with the name "STP" (allegedly short for "Serenity, Tranquility, and Peace") in the Haight-Ashbury district in San Francisco. This occurred due to DOM being publicly distributed for free in the form of high-dose tablets by LSD distributor Owsley Stanley, who had personally learned of DOM from Shulgin.{{cite journal | vauthors = Trout K, Daley PF | title = The origin of 2,5-dimethoxy-4-methylamphetamine (DOM, STP) | journal = Drug Test Anal | volume = 16 | issue = 12 | pages = 1496–1508 | date = December 2024 | pmid = 38419183 | doi = 10.1002/dta.3667 | url = 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}} It is unclear why Shulgin provided information about DOM to Stanley, since doing so had the potential to risk Shulgin's professional career and the DOET clinical studies. One possibility is that Dow Chemical Company was not further looking into DOM and Shulgin thought that it was a promising drug that would otherwise be forgotten. In any case, street use of DOM was short-lived because the tablets caused a public health crisis due to them often producing very long durations (up to 3–4{{nbsp}}days), intense experiences, worrying physical side effects, and hospitalizations. DOM was first reported on in the media and scientific literature in 1967 as a result of the crisis.{{cite journal | vauthors = Snyder SH, Faillace L, Hollister L | title = 2,5-dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug | journal = Science | volume = 158 | issue = 3801 | pages = 669–670 | date = November 1967 | pmid = 4860952 | doi = 10.1126/science.158.3801.669 | bibcode = 1967Sci...158..669S | url = }}{{cite journal | vauthors = Snyder SH, Faillace LA, Weingartner H | title = DOM (STP), a new hallucinogenic drug, and DOET: effects in normal subjects | journal = Am J Psychiatry | volume = 125 | issue = 3 | pages = 113–120 | date = September 1968 | pmid = 4385937 | doi = 10.1176/ajp.125.3.357 | url = }} DOM became illegal in the United States in 1968.

Dow Chemical Company terminated its clinical research program on DOET due to the DOM public health crisis. DOET was subsequently first described in the literature by Snyder and colleagues in 1968. Snyder continued to be interested in DOET as a potential medicine, but it was never further developed. Snyder also described 2,5-dimethoxyamphetamine (2,5-DMA), which had been synthesized and tested by Shulgin, in the literature in 1968.{{cite journal | vauthors = Snyder SH, Richelson E | title = Psychedelic drugs: steric factors that predict psychotropic activity | journal = Proc Natl Acad Sci U S A | volume = 60 | issue = 1 | pages = 206–213 | date = May 1968 | pmid = 5241523 | pmc = 539103 | doi = 10.1073/pnas.60.1.206 | doi-access = free | bibcode = 1968PNAS...60..206S | url = | quote = Shulgin (personal communication) has synthesized 2,5-dimethoxyamphetamine (2,5-DMA) (Fig. 4) and observed its potency in man as between 8 and 10 MU. This compound corresponds to TMA-2 with the absence of the methoxy at C-4. 2,5-DMA is considerably more potent than TMA, TMA-3, or TMA-4, all of which have three methoxy groupings. [...] }} DOM and DOET were further described in the scientific literature by Shulgin in 1969.{{cite journal | last=Shulgin | first=Alexander T. | title=Psychotomimetic Agents Related to the Catecholamines | journal=Journal of Psychedelic Drugs | volume=2 | issue=2 | date=1969 | issn=0022-393X | doi=10.1080/02791072.1969.10524409 | pages=14–19}} In addition, Shulgin discussed DOM, DOET, TMA-2, and 2,5-DMA in a book chapter on hallucinogens published in 1970.{{cite book | author = Alexander Shulgin | chapter = Chemistry and Structure-Activity Relationships of the Psychotomimetics | editor = D. H. Efron | title = Psychotomimetic Drugs | publisher = Raven Press | location = New York | pages = 21–41 | date = 1970 | url = https://www.erowid.org/library/books_online/psychotomimetic_drugs.pdf#page=23 }}

The earlier DOx drugs like DOM and DOET were subsequently followed by DOB, which was developed by Shulgin and colleagues like Claudio Naranjo, in 1971,{{cite journal | vauthors = Shulgin AT, Sargent T, Naranjo C | title = 4-Bromo-2,5-dimethoxyphenylisopropylamine, a new centrally active amphetamine analog | journal = Pharmacology | volume = 5 | issue = 2 | pages = 103–107 | date = 1971 | pmid = 5570923 | doi = 10.1159/000136181 | url = }} and by DOI, DOC, and a few other analogues, which were developed by another research group, in 1973.{{cite journal | last1=Coutts | first1=Ronald T. | last2=Malicky | first2=Jerry L. | title=The Synthesis of Some Analogs of the Hallucinogen 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM) | journal=Canadian Journal of Chemistry | volume=51 | issue=9 | date=1 May 1973 | issn=0008-4042 | doi=10.1139/v73-210 | doi-access=free | pages=1402–1409 }} After this, numerous other DOx drugs were synthesized and characterized, both by Shulgin and other scientists.{{cite book | veditors = Iversen LL, Iversen SD, Snyder SH | last=Shulgin | first=Alexander T. | title=Stimulants | chapter=Psychotomimetic Drugs: Structure-Activity Relationships | publisher=Springer US | publication-place=Boston, MA | date=1978 | isbn=978-1-4757-0512-6 | doi=10.1007/978-1-4757-0510-2_6 | pages=243–333 | chapter-url=https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6 | url=https://books.google.com/books?id=h0_uBwAAQBAJ&pg=PA261 | quote=3,4,5-Trimethoxyphenylisopropylamine (33, TMA, trimethoxyamphetamine) is the first psychotomimetic drug that evolved from the systematic application of the principles discovered in studying the relationships between chemical structure and biological activity. Armed with the known structure of mescaline, the proclivity of most phenethylamines to be of only fleeting activity centrally (due to facile deamination), and the effectiveness of a methyl group alpha- to the nitrogen as a stabilizing factor in central activity, Her (1947) synthesized TMA. His favorable impressions on the euphoric properties of the compound encouraged the Canadian group of Peretz and co-workers (1955) to explore its psychopharmacological nature and to evaluate its potential as a psychotomimetic. [...] 3.1.6. 2,4,5-Trimethoxyphenylisopropylamine This geometric isomer of TMA was first synthesized by Bruckner (1933) and its psychotomimetic properties were first observed some 30 years later (Shulgin, 1964a), 2,4,5-Trimethoxyphenylisopropylamine (34, TMA-2, 2,4,5-trimethoxyamphetamine) was the second of the six possible positional isomers found to be psychotomimetic, and was thus called TMA-2. }}{{cite book | vauthors = Nichols DE, Glennon RA | date = 1984 | chapter = Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens | veditors = Jacobs BL | title = Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives | pages = 95–142 | publisher = Raven Press | location = New York | isbn = 978-0-89004-990-7 | oclc = 10324237 | url = https://books.google.com/books?id=EdpsAAAAMAAJ&pg=PA95 | chapter-url = https://bitnest.netfirms.com/external/Books/HallucinogensNBCP95 }}{{cite book | last1=Shulgin | first1=A.T. | last2=Shulgin | first2=A. | title=PiHKAL: A Chemical Love Story | publisher=Transform Press | year=1991 | isbn=978-0-9630096-0-9 | url=https://books.google.com/books?id=O8AdHBGybpcC | access-date=2 November 2024 }}{{cite book | last1=Shulgin | first1=A. | last2=Manning | first2=T. | last3=Daley | first3=P.F. | title=The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds | publisher=Transform Press | location=Berkeley | volume=1 | year=2011 | isbn=978-0-9630096-3-0 | url=https://books.google.com/books?id=68-huAAACAAJ | access-date=2 November 2024 | quote = A short history of DOM (STP) notes that the original synthesis took place in 1963, psychological effects were discovered the following year, and that the compound had appeared in the Haight-Ashbury scene of mid-1967 (Shulgin, 1977b). The known congeners of DOM were reviewed for structure-activity relationships (Barfknecht et al., 1978). [...] Shulgin, AT. (1977b) Profiles of psychedelic drugs. 5. STP. J. Psych. Drugs 9(2): 171-172. }}{{cite book | vauthors = Nichols DE | title = Chemistry and Structure-Activity Relationships of Psychedelics | series = Current Topics in Behavioral Neurosciences | volume = 36 | pages = 1–43 | date = 2018 | pmid = 28401524 | doi = 10.1007/7854_2017_475 | isbn = 978-3-662-55878-2 | url = }}

Following its discovery, DOI has become widely used in scientific research in the study of the serotonin 5-HT₂ receptors.

The DOx family includes the following members:

{{Sticky}}

{{See also|4C (psychedelics)}}

A number of additional compounds are known with alternative substitutions:

{{Sticky}}

• 2,5-Dimethoxyamphetamine
• Substituted mescaline analogue
• 2Cs, 4Cs, 25-NB, FLY
• Substituted amphetamines
• Substituted benzofurans
• Substituted cathinones
• Substituted methoxyphenethylamine
• Substituted methylenedioxyphenethylamines
• Substituted phenethylamines
• Substituted tryptamines
• PiHKAL
• The Shulgin Index

{{Reflist}}

• [http://isomerdesign.com/PiHKAL/ PiHKAL ("Phenethylamines I Have Known And Loved")] by Alexander "Sasha" Shulgin (1991)
• [https://psychonautwiki.org/wiki/DOx DOx - PsychonautWiki]
• [https://tripsitter.com/dox/ Category: DOX - Tripsitter]

{{Psychedelics}}

{{Serotonin receptor modulators}}

{{TAAR modulators}}

{{Phenethylamines}}

{{Chemical classes of psychoactive drugs}}

{{DEFAULTSORT:Dox}}

Category:Chemical classes of psychoactive drugs

Category:DOx (psychedelics)