2,5-Dimethoxy-4-bromoamphetamine

Chemical compound ly November 2024 vanc 6 verified verified 477192160 DOB Brolamfetamine DOB-racemic-skeletal.svg skin-invert-image 200px Chemical structure of (±)-DOB DOB-3d-sticks.png bg-transparent 175px Ball-and-stick model of (R)-DOB Oral Serotonin 5-HT2 receptor agonist; Serotonergic psychedelic; Hallucinogen None Schedule 9 F2 Anvisa Brazilian Health Regulatory Agency 2023-07-24 RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 live https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 2023-08-27 2023-08-27 Diário Oficial da União pt-BR 2023-07-25 Schedule I Class A Schedule I P I 1–2 hoursPeak: 3–4 hours 18–36 hours correct CAS 64638-07-9 (racemate)43061-15-0 (R-isomer)43061-16-1 (S-isomer) 62065 46507989 155 correct drugbank DB01484 correct chemspider 55902 correct FDA 67WJC4Y2QY D12707 correct EBI 6607 DOB; 4-Bromo-2,5-dimethoxyamphetamine; Brolamfetamine; Brolamphetamine; Bromo-DMA; 2,5-Dimethoxy-4-bromo-α-methylphenethylamine; 4-Bromo-2,5-dimethoxyphenyl-isopropylamine 1-(4-bromo-2,5-dimethoxyphenyl)propan-2-amine 11 16 1 1 2 CC(CC1=CC(=C(C=C1OC)Br)OC)N correct chemspider 1S/C11H16BrNO2/c1-7(13)4-8-5-11(15-3)9(12)6-10(8)14-2/h5-7H,4,13H2,1-3H3 correct chemspider FXMWUTGUCAKGQL-UHFFFAOYSA-N 63-65 (207–208 °C hydrochloride) 2,5-Dimethoxy-4-bromoamphetamine (DOB), also known as brolamfetamine (INN International Nonproprietary Name),World Health Organization International Nonproprietary Names (INN) for Pharmaceutical Substances https://books.google.com/books?id=HcogPwAACAAJ 2000 World Health Organization 978-0-11-986227-0 is a psychedelic drug of the phenethylamine, amphetamine, and DOx families. Shulgin A Profiles of Psychedelic Drugs: 10. DOB J Psychoactive Drugs 13 1 99 1981 7277091 10.1080/02791072.1981.10471457 https://bibliography.maps.org/resources/download/8845 https://web.archive.org/web/20250712232007/https://bibliography.maps.org/resources/download/8845 12 July 2025 For many years, prior to the discovery of newer compounds, DOB was the most potent known phenethylamine psychedelic. It is taken orally. The drug acts as an agonist of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A receptor. Analogues of DOB include 2C-B, DOM, DOI, and Bromo-DragonFLY (DOB-DFLY), among others. DOB was first synthesized by Alexander Shulgin in 1967 and was described by him and his colleagues in the scientific literature in 1971.Erowid Online Books: "PiHKAL" - #62 DOB Shulgin AT, Sargent T, Naranjo C 4-Bromo-2,5-dimethoxyphenylisopropylamine, a new centrally active amphetamine analog Pharmacology 5 2 103–107 1971 5570923 10.1159/000136181 46844380 http://repositorio.uchile.cl/handle/2250/162196 Shulgin subsequently further described the effects of DOB in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). Use and effects In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists DOB's dose as 1 to 3mg orally and its duration as 18 to 30hours. In an earlier publication, he listed its dose as 2 to 3mg for racemic DOB and 1 to 2mg for the preferentially active (R)-DOB enantiomer. In addition, he described the duration as being extremely long, with a gradual descent and baseline being achieved after 24 to 36hours. The onset has been described as 1 to 2hours, the time to peak as 3 or 4hours, and a plateau occurring from 4 to 10hours. Its onset is said to be relatively slow. The effects of DOB and (R)-DOB have been reported to include visual changes such as prismatic-colored rings around the moon and long-lasting "after-images" following seeing points of light, little visual distortion, an "incredible Moebius strip representation of reality at the intellectual level", rich fantasy, flashes of depersonalization, cosmic thinking, introspection, insights, intoxication, impairment, stimulation, brief lapses in attention or "little fugue states", body load, cramps, muscle tremors, and sleep disruption. At a low dose of 0.4mg DOB, there was only enhanced visual perception, strengthening of colors, enriched emotional affect, a comfortable good feeling, and colorful and important dreams. (R)-DOB produced moderate effects at a dose of 0.5mg and pronounced effects at 1.0 to 1.5mg, whereas there were no effects with 0.5mg (S)-DOB and only threshold and very slight effects with 1.0mg (S)-DOB. In relation to this, (R)-DOB is described as the more active enantiomer and (S)-DOB as much less active. In one report, 1mg (R)-DOB was described as not as strong as 2mg DOB, suggesting that it is more potent than the racemate but is not double its potency and hence that (S)-DOB also contributes to the effects of the racemate. (S)-DOB has never been tested up to fully active doses. In another source however, by Richard Glennon and colleagues, the approximate hallucinogenic dose was listed as 0.8 to 2.0mg for racemic DOB, 0.5mg for (R)-DOB, and 5.0mg for (S)-DOB. Glennon RA, Rosecrans JA Indolealkylamine and phenalkylamine hallucinogens: a brief overview Neurosci Biobehav Rev 6 4 489–497 1982 6757811 10.1016/0149-7634(82)90030-6 Side effects Side effects of DOB include body load, muscle tremors, muscle cramps, attention lapses described as "little fugue states", sleeping difficulties, and bizarre dreams. Overdose Overdose of DOB has been reported to produce cardiovascular symptoms, convulsions, coma, and death. Excessively high doses of DOB may cause diffuse arterial spasm. Bowen JS, Davis GB, Kearney TE, Bardin J Diffuse vascular spasm associated with 4-bromo-2,5-dimethoxyamphetamine ingestion JAMA 249 11 1477–1479 March 1983 6827726 10.1001/jama.1983.03330350053028 The vasospasm responded readily to intra-arterial and intravenous vasodilators, such as tolazoline. A 35mg overdose resulted in death, while a 75mg overdose in a person with tolerance resulted in ergotism-like complications that required amputation. Interactions Psychedelic drug#Interactions Trip killer#Serotonergic psychedelic antidotes DOB may interact synergistically with alcohol. Pharmacology Pharmacodynamics + DOB activities Target Affinity (Ki, nM) 5-HT1A 2,550–7,904 5-HT1B 941 5-HT1D 636 5-HT1E 556–1,427 5-HT1F ND No data 5-HT2A 0.6–81 (Ki)0.52–50 (EC50 half-maximal effective concentration)57–105% (Emax maximal efficacy) 5-HT2B 2.9–44 (Ki)2.82–65 (EC50 half-maximal effective concentration)70–100% (Emax maximal efficacy) 5-HT2C 1.3–78 (Ki)0.25–102 (EC50 half-maximal effective concentration)58–112% (Emax maximal efficacy) 5-HT3 >10,000 5-HT4 ND No data 5-HT5A 5,311 5-HT6 5,535 5-HT7 506 α1A, α1B >10,000 α1D ND No data α2A 4,266 α2B 1,527 α2C 594 β1 2,425 β2 303 D1, D2 >10,000 D3 808 D4, D5 >10,000 H1 9,120 H2–H4 >10,000 M1, M2 >10,000 M3 1,152 M4, M5 >10,000 TAAR1 >1,000 I1 1,596 σ1 2,193 σ2 >10,000 SERT Serotonin transporter 8,538 (Ki) NET Norepinephrine transporter >10,000 (Ki) DAT Dopamine transporter >10,000 (Ki) MAO-A Monoamine oxidase A 100,000 (IC50 half-maximal inhibitory concentration) (rat) MAO-B Monoamine oxidase B >100,000 (IC50 half-maximal inhibitory concentration) (rat) Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: PDSP Database UNC https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=dob&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query zu 4 February 2025 Liu T BindingDB BDBM50005257 (+)-2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::(+)2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::(+/-)2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::(-)-2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::(-)2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::1-(4-bromo-2,5-dimethoxyphenyl)propan-2-amine::2-(2-Methoxy-phenyl)-1-methyl-ethylamine::2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine((-)-DOB)::2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine((R)-(-)-DOB)::2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine((S)-(+)-DOB)::2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine(DOB)::2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine[R(-)DOB]::2-(5-Bromo-2,4-dimethoxy-phenyl)-1-methyl-ethylamine::Brolamfetamine::CHEMBL6607::DOB::Racemic DOB BindingDB https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50005257 4 February 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 van Wijngaarden I, Soudijn W Pharmacochemistry Library 5-HT2A, 5-HT2B and 5-HT2C receptor ligands Elsevier 27 1997 978-0-444-82041-9 10.1016/s0165-7208(97)80013-x 161–197 Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors Br J Pharmacol 136 4 510–519 June 2002 12055129 1573376 10.1038/sj.bjp.0704747 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 Frontiers in Pharmacology 14 1101290 2023 36762110 9902381 10.3389/fphar.2023.1101290 free Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK Amphetamine Derivatives as Monoamine Oxidase Inhibitors Front Pharmacol 10 1590 2019 32038257 6989591 10.3389/fphar.2019.01590 free Scorza MC, Carrau C, Silveira R, Zapata-Torres G, Cassels BK, Reyes-Parada M Monoamine oxidase inhibitory properties of some methoxylated and alkylthio amphetamine derivatives: structure-activity relationships Biochem Pharmacol 54 12 1361–1369 December 1997 9393679 10.1016/s0006-2952(97)00405-x https://repositorio.uchile.cl/handle/2250/157599 Rudin D, Luethi D, Hoener MC, Liechti ME Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues The FASEB Journal 36 S1 2022 fasebj.2022.36.S1.R2121 0892-6638 10.1096/fasebj.2022.36.S1.R2121 free https://www.researchgate.net/publication/360423277 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 DOB is a serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist. Its psychedelic effects are mediated by its agonistic properties at the 5-HT2A receptor. Due to its selectivity, DOB is often used in scientific research when studying the 5-HT2 receptor subfamily. It is a very weak agonist of the human trace amine-associated receptor 1 (TAAR1) and a weak agonist of the rhesus monkey TAAR1. Lewin AH, Miller GM, Gilmour B 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 22037049 3236098 10.1016/j.bmc.2011.10.007 In contrast to the serotonin releasing agent MDMA, DOB does not produce protein kinase C (PKC) activation in the brains of rodents in vivo. Kramer HK, Poblete JC, Azmitia EC Activation of protein kinase C (PKC) by 3,4-methylenedioxymethamphetamine (MDMA) occurs through the stimulation of serotonin receptors and transporter Neuropsychopharmacology 17 3 117–129 September 1997 9272479 10.1016/S0893-133X(97)00026-2 Kenneth H Evidence for the involvement of the serotonin uptake transporter and the serotonin-2 receptor in the activation of protein kinase C (PKC) by substituted amphetamines in the adult rodent brain 1996 ProQuest New York University https://www.proquest.com/openview/7fd77d32ea08d8335780ab0d4409b427/1?pq-origsite=gscholar&cbl=18750&diss=y 1 February 2025 MDMA manifests its acute psychotropic and neurotoxic effects by releasing 5-HT from nerve endings. MDMA also shows a moderate agonist-like affinity (1.5-3.2 mM [(sic)]) for the central 5-HT2 receptor. Activation of this receptor stimulates the translocation/activation of protein kinase C (PKC) and the release of Ca2+ from intracellular sequestration sites. MDMA has already been shown to increase [Ca2+], and this may proceed through the activation of this receptor. [...] In vivo, both MDMA and PCA were found to produce a lasting translocation of [protein kinase C (PKC)] in the cortex and hippocampus of treated rats. Fluoxetine, a 5-HT uptake inhibitor, prevents PKC translocation, while ketanserin, a 5-HT2A antagonist, acts similarly but a diminished efficacy. Non-neurotoxic drugs like fluoxetine, DOB, and cocaine were devoid of MDMA's long-term PKC translocating abilities, and suggests that receptor stimulation alone is not the sole mechanism. In synaptosomes, MDMA was effective at producing PKC translocation by binding to the 5-HT uptake carner. This in vitro response [of] fluoxetine reverses this response and demonstrates that MDMA translocates PKC within the 5-HT nerve terminal. The PKC activation by MDMA appears to be dependent on uptake by the serotonin transporter (SERT). DOB has been found to reduce aggression in rats. Morrison TR, Melloni RH Neuroscience of Aggression The role of serotonin, vasopressin, and serotonin/vasopressin interactions in aggressive behavior Curr Top Behav Neurosci 17 189–228 2014 24496652 10.1007/7854_2014_283 978-3-662-44280-7 Another 5HT2A receptor partial agonist, DOB, has a marginally higher affinity for the 5HT2A receptor (in its low affinity state) than DOI (Roth et al. 1997), and in the water competition (WC) test it has been shown to block defensive aggression in rats. Interestingly, DOI also reduced the number of offensive aggressive behaviors (i.e., attacks, greater latency to first attack, shorter attack duration) in the same animals that exhibited DOI-induced reductions in defensive behaviors during the WC test (Muehlenkamp et al. 1995). Muehlenkamp F, Lucion A, Vogel WH Effects of selective serotonergic agonists on aggressive behavior in rats Pharmacology Biochemistry and Behavior 50 4 671–674 April 1995 7617717 10.1016/0091-3057(95)00351-7 12774131 DOB is one of the most potent compounds in PiHKAL; while the active dose is similar to that of DOI, another psychedelic amphetamine, DOB has been shown to have a higher efficacy in triggering downstream effects mediated by serotonin 5-HT2 receptors. Parrish JC, Braden MR, Gundy E, Nichols DE Differential phospholipase C activation by phenylalkylamine serotonin 5-HT 2A receptor agonists Journal of Neurochemistry 95 6 1575–1584 December 2005 16277614 10.1111/j.1471-4159.2005.03477.x 24005602 free Chemistry thumb|right|upright|Tabs of DOB, confiscated by police in Concord, California in 2006. The full name of the chemical is 2,5-dimethoxy-4-bromoamphetamine. DOB has a stereocenter and R-(−)-DOB is the eutomer. This is an important finding as it is suggestive that it is targeting different receptors relative to most other phenethylamines (e.g. MDMA) where the R-isomer serves as the distomer. Synthesis The chemical synthesis of DOB has been described. Analogues Omission of the amphetamine related α-methyl leads to 2C-B, a compound that possesses a lower affinity for the 5-HT2A receptor and is a weaker receptor agonist.December 2017 Other analogues of DOB include 4C-B, Bromo-DragonFLY, DOB-FLY, DOB-5-hemiFLY, and 25B-NBOMe, among others. History DOB was first synthesized by Alexander Shulgin in 1967. It was first described in the scientific literature in a paper by Shulgin, Claudio Naranjo, and another colleague in 1971. The INN International Nonproprietary Name of DOB, brolamfetamine, was proposed and recommended by the World Health Organization (WHO) in 1986.INN Proposed List 55 World Health Organization (WHO) 9 April 1986 https://www.who.int/publications/m/item/inn-pl-55 World Health Organization (WHO) 1900 3 November 2024INN Recommended List 26 World Health Organization (WHO) 9 June 1986 https://www.who.int/publications/m/item/inn-rl-26 World Health Organization (WHO) 1900 3 November 2024 This was the same year that the Multidisciplinary Association for Psychedelic Studies (MAPS) was founded. Emerson A, Ponté L, Jerome L, Doblin R History and future of the Multidisciplinary Association for Psychedelic Studies (MAPS) J Psychoactive Drugs 46 1 27–36 2014 24830183 10.1080/02791072.2014.877321 https://www.researchgate.net/publication/262381557 DOB was registered with the WHO as a supposed "anorexic" (appetite suppressant). ((World Health Organization)) Use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances, 2024 World Health Organization 2024 https://iris.who.int/bitstream/handle/10665/379226/9789240099388-eng.pdf#page=158 21 October 2024 152–153 Society and culture Legal status Internationally, DOB is a Schedule I substance under the Convention on Psychotropic Substances and the drug is legal only for medical, industrial or scientific purposes.http://www.incb.org/pdf/e/list/green.pdf List of psychotropic substances under international control 30 March 2007 https://web.archive.org/web/20070302130637/http://www.incb.org/pdf/e/list/green.pdf 2 March 2007 dead Canada Listed as a Schedule 1 as it is an analogue of amphetamine. (15) 4-Bromo-2,5-dimethoxyamphetamine (4-Bromo-2,5-dimethoxy-α-methylbenzeneethanamine) http://isomerdesign.com/Cdsa/schedule.php?schedule=3&section=1&structure=C https://web.archive.org/web/20211123123506/http://isomerdesign.com/Cdsa/schedule.php?schedule=3&section=1&structure=C 2021-11-23 Isomer Design Australia DOB is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (February 2017). Department of Health and Aged Care Federal Register of Legislation Australian Government Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534 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. Russia Schedule I, possession of at least 10 mg is a criminal offence.http://base.garant.ru/70237124/ Постановление Правительства РФ от 01.10.2012 N 1002 Об утверждении значительного, крупного и особо крупного размеров наркотических средств и психотропных веществ, а также значительного, крупного и особо крупного размеров для растений, содержащих наркотические средства или психотропные вещества, либо их частей, содержащих наркотические средства или психотропные вещества, для целей статей 228, 228.1, 229 и 229.1 Уголовного кодекса Российской Федерации Resolution of the Government of the Russian Federation of 01.10.2012 N 1002 On approval of significant, large and especially large sizes of narcotic drugs and psychotropic substances, as well as significant, large and especially large sizes for plants containing narcotic drugs or psychotropic substances, or their parts containing narcotic drugs or psychotropic substances, for the purposes of Articles 228, 228.1, 229 and 229.1 of the Criminal Code of the Russian Federation ru United Kingdom DOB is a Class A drug in the United Kingdom under the Misuse of Drugs Act 1971. United States DOB is a Schedule I controlled substance under federal law in the United States. Shulgin A, Manning T, Daley PF The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds Transform Press Berkeley 1 2011 978-0-9630096-3-0 102 It was scheduled in 1973. Bartels Jr JR September 14, 1973 Part 308 – Schedules of Controlled Substances; Additions to Schedule I Federal Register 38 183 26447–8 Drug Enforcement Administration https://isomerdesign.com/Cdsa/FR/38FR26447.pdf September 30, 2023 Isomer Design https://web.archive.org/web/20220303023114/https://isomerdesign.com/Cdsa/FR/38FR26447.pdf March 3, 2022 See also DOx (psychedelics) References External links DOB - Isomer Design DOB - PsychonautWiki DOB - Erowid DOB - TripSit The Big & Dandy DOB Thread - Bluelight DOB - PiHKAL - Erowid DOB - PiHKAL - Isomer Design DOB - The Shulgin Index Category:5-HT2A agonists Category:5-HT2B agonists Category:5-HT2C agonists Category:Bromobenzene derivatives Category:Designer drugs Category:DOx (psychedelics) Category:PiHKAL Category:Serotonin receptor agonists Category:TAAR1 agonists