2,5-Dimethoxy-4-isobutylamphetamine

vanc 6 DOIB DOiB structure.svg skin-invert-image 250px Oral Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen; Anti-inflammatory drug None 89556-64-9 44374984 23231800 161299 2,5-Dimethoxy-4-isobutylamphetamine; 4-Isobutyl-2,5-dimethoxyamphetamine; DOIB; DOiBu; 2,5-Dimethoxy-4-(2-methylpropyl)amphetamine 1-[2,5-dimethoxy-4-(2-methylpropyl)phenyl]propan-2-amine 15 25 1 2 CC(C)CC1=CC(=C(C=C1OC)CC(C)N)OC 1S/C15H25NO2/c1-10(2)6-12-8-15(18-5)13(7-11(3)16)9-14(12)17-4/h8-11H,6-7,16H2,1-5H3 ZLESHKOTWSWEGW-UHFFFAOYSA-N 2,5-Dimethoxy-4-isobutylamphetamine (DOIB or DOiBu) is a serotonin 5-HT2A receptor agonist, serotonergic psychedelic, and anti-inflammatory drug of the phenethylamine, amphetamine, and DOx families. Nichols DE Structure–activity relationships of serotonin 5-HT2A agonists Wiley Interdisciplinary Reviews: Membrane Transport and Signaling 1 5 2012 2190-460X 10.1002/wmts.42 free 559–579 A comparison of two isomeric 4-butyl groups in this series (Figure [19]) revealed that 2,5-dimethoxy-4-isobutylamphetamine 44 retained significant activity in a drug discrimination task, in rats trained to discriminate LSD from saline, whereas the 2-butyl homolog was about one third less potent than the isobutyl and also failed to produce full substitution in the rats. [...] FIGURE 19 | Potential 5-HT2A (5-hydroxytryptamine) receptor agonists with an isomeric 4-butyl ring substituent. [...] Nichols DE Chemistry and Structure-Activity Relationships of Psychedelics Current Topics in Behavioral Neurosciences 36 1–43 2018 28401524 10.1007/7854_2017_475 978-3-662-55878-2 If the 4-substituent is an alkyl group, branching adjacent to the aromatic ring is not tolerated. For example, 2,5-dimethoxy-4-isobutylamphetamine 46 (DOIB) demonstrated significant activity in a rat drug discrimination task, in animals trained to discriminate LSD from saline. DOIB had only about one-third the activity of DOM in humans, with a dose in the 10 to 15 mg range (Shulgin and Shulgin 1991). By contrast, the 2-butyl homolog was about one-third less potent, but also failed to produce full substitution in the rats. The active oral dose in man is reported to be 25–30 mg (Shulgin and Shulgin 1991). [...] Large bulky alkyl groups at the 4-position, such as isopropyl or tert-butyl, lead to inactive compounds (Glennon et al. 1981, 1982a; Glennon and Rosecrans 1982; Oberlender et al. 1984). Not surprisingly, therefore, aryl groups attached at the 4-position also gave antagonists, generally with low affinity (Trachsel et al. 2009). Interestingly, however, when a 3-phenylpropyl substituent was introduced at this position, the compound was reported to be a weak partial agonist (Dowd et al. 2000). Shulgin AT, Shulgin A #63 DOBU 2,5-DIMETHOXY-4-(n)-BUTYLAMPHETAMINE https://erowid.org/library/books_online/pihkal/pihkal063.shtml PiHKAL: A Chemical Love Story 1991 Transform Press 1st Berkeley, CA 978-0-9630096-0-9 25627628 https://books.google.com/books?id=O8AdHBGybpcC In drug discrimination studies in rats, DOIB was only a third as active as DOM, and in humans the activity falls in the 10 to 15 milligram area. Shulgin A, Manning T, Daley PF #60. DOM 118–129 https://archive.org/details/shulgin-index-vol-1/page/118/mode/1up The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds Transform Press Berkeley, CA 1 2011 978-0-9630096-3-0 709667010 DOM, DOIB, and DOSB were compared in discrimination studies based on training with LSD (Oberlender et al., 1984). [...] Homologues: [...] DOIB: [...] Ref: (17-20) [...] (17) Animal discrimination studies based on LSD (Oberlender et al., 1984). (18) Synthesis (Oberlender et al., 1984). (19) Serotonin receptor affinities determined in isolated rat fundus preparation, and studies in rats trained to discriminate 5-MeO-DMT from saline (Glennon et al., 1981b). Use and effects DOIB is active at doses of 10 to 15mg orally, and hence is about one-third as potent as DOM. Shulgin AT Basic Pharmacology and Effects 67–137 Laing RR Hallucinogens: A Forensic Drug Handbook Elsevier Science Forensic Drug Handbook Series 2003 978-0-12-433951-4 https://books.google.com/books?id=l1DrqgobbcwC https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 1 February 2025 Jacob P, Shulgin AT Structure-activity relationships of the classic hallucinogens and their analogs NIDA Res Monogr 146 74–91 1994 8742795 https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 https://web.archive.org/web/20230805004551/https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 dead August 5, 2023 Nichols DE, Glennon RA 1984 Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens Jacobs BL Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives 95–142 Raven Press New York 978-0-89004-990-7 10324237 https://books.google.com/books?id=EdpsAAAAMAAJ&pg=PA95 https://bitnest.netfirms.com/external/Books/HallucinogensNBCP95 Interactions Psychedelic drug#Interactions Trip killer#Serotonergic psychedelic antidotes Pharmacology Pharmacodynamics DOIB is a full agonist of the serotonin 5-HT2A receptor, with an EC50 half-maximal effective concentration of 12.6nM and an Emax maximal efficacy of 98.8%, both for calcium mobilization. It is about one-third as potent as DOM in rodent drug discrimination tests and also substitutes for LSD in these tests. Oberlender RA, Kothari PJ, Nichols DE, Zabik JE Substituent branching in phenethylamine-type hallucinogens: a comparison of 1-[2,5-dimethoxy-4-(2-butyl)phenyl]-2-aminopropane and 1-[2,5-dimethoxy-4-(2-methylpropyl)phenyl]-2-aminopropane J Med Chem 27 6 788–792 June 1984 6737421 10.1021/jm00372a015 https://chemistry.mdma.ch/hiveboard/rhodium/pdf/nichols/nichols-branched.4-substituents.pdf In addition to its psychedelic effects, DOIB has highly potent anti-inflammatory effects in preclinical research. Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore ACS Pharmacol Transl Sci 4 2 488–502 April 2021 33860179 8033619 10.1021/acsptsci.0c00063 https://www.researchgate.net/publication/360537036 The nature of the 4-position substituent of phenethylamine psychedelics has been previously linked to 5-HT2 receptor selectivity as well as agonist properties at 5-HT2 receptors.40 Analysis of the 40position demonstrated that the identity of the moiety at this position was rather flexible. Fully efficacious substitutions at the 4-position included the halogens iodine and bromine (R)-DOI (Figure 3), 2C-B (Figure 7A), methoxy (TMA-2) (Figure 7G), short-chain hydrocarbons (R)-DOM (Figure 7H), (R)-DOET) (Figure 7I), and a branched hydrocarbon (DOiBu) (Figure 7J). [...] In a comparison of PenH-AUC values determined for each drug as a proxy measure of anti-inflammatory efficacy (Figure 8A) to either EC50 or Emax for calcium mobilization downstream of 5-HT2A receptor activation (Table 1), [...] It was more potent than almost any other tested psychedelic. The drug was notably more potent than (R)-DOI, but was less potent than 2C-I (the most potent assessed compound). Chemistry Synthesis The chemical synthesis of DOIB has been described. Analogues DOIB is part of the series of straight-chain and branched-chain 4-alkylated DOx drugs that also includes DOM, DOET, DOPR, DOBU, DOAM, and DOHx, among others. Some other notable analogues of DOIB include DOBU (n-butyl), DOSB (sec-butyl), and DOTB (tert-butyl). thumb|none|550px|class=skin-invert-image|DOIB, DOSB, and DOTB. Society and culture Legal status Canada DOIB is a controlled substance in Canada under phenethylamine blanket-ban language.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 See also DOx (psychedelics) 2C-iBu (ELE-02) 5-HT2A receptor § Anti-inflammatory effects References External links DOIB - Isomer Design Category:5-HT2A agonists Category:Anti-inflammatory agents Category:DOx (psychedelics) Category:Isobutyl compounds Category:Psychedelic phenethylamines Category:Serotonin receptor agonists