2,5-Dimethoxy-4-isobutylamphetamine

{{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | drug_name = DOIB | image = DOiB structure.svg | image_class = skin-invert-image | width = 250px | caption =

| legal_status =

| IUPAC_name = 1-[2,5-dimethoxy-4-(2-methylpropyl)phenyl]propan-2-amine | C=15 | H=25 | N=1 | O=2 | SMILES = CC(C)CC1=CC(=C(C=C1OC)CC(C)N)OC | StdInChI = 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 | StdInChIKey = 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.<ref name="Nichols2012">{{cite journal | vauthors = Nichols DE | title=Structure–activity relationships of serotonin 5-HT2A agonists | journal=Wiley Interdisciplinary Reviews: Membrane Transport and Signaling | volume=1 | issue=5 | date=2012 | issn=2190-460X | doi=10.1002/wmts.42 | doi-access=free | pages=559–579 | quote=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 <nowiki>|</nowiki> Potential 5-HT2A (5-hydroxytryptamine) receptor agonists with an isomeric 4-butyl ring substituent. [...]}}</ref><ref name="Nichols2018">{{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 = | quote = 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).}}</ref><ref name="PiHKAL">{{cite book | vauthors = Shulgin AT, Shulgin A | chapter = #63 DOBU 2,5-DIMETHOXY-4-(n)-BUTYLAMPHETAMINE | pages = | chapter-url = https://erowid.org/library/books_online/pihkal/pihkal063.shtml | title = PiHKAL: A Chemical Love Story | date = 1991 | publisher = Transform Press | edition = 1st | location = Berkeley, CA | isbn = 978-0-9630096-0-9 | oclc = 25627628 | url = https://books.google.com/books?id=O8AdHBGybpcC | quote = 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. }}</ref><ref name="ShulginManningDaley2011">{{cite book | vauthors = Shulgin A, Manning T, Daley PF | chapter = #60. DOM | pages = 118–129 | chapter-url = https://archive.org/details/shulgin-index-vol-1/page/118/mode/1up | title = The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds | publisher = Transform Press | location = Berkeley, CA | volume = 1 | year = 2011 | isbn = 978-0-9630096-3-0 | oclc = 709667010 | quote = 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). }}</ref><ref name="FlanaganBillacLandry2021" />

==Use and effects== DOIB is active at doses of 10 to 15{{nbsp}}mg orally, and hence is about one-third as potent as DOM.<ref name="Nichols2018" /><ref name="PiHKAL" /><ref name="Shulgin2003">{{cite book | vauthors = Shulgin AT | chapter=Basic Pharmacology and Effects | pages=67–137 | veditors = Laing RR | title=Hallucinogens: A Forensic Drug Handbook | publisher=Elsevier Science | series=Forensic Drug Handbook Series | year=2003 | isbn=978-0-12-433951-4 | url=https://books.google.com/books?id=l1DrqgobbcwC | chapter-url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 | access-date=1 February 2025}}</ref><ref name="JacobShulgin1994">{{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 | archive-url = https://web.archive.org/web/20230805004551/https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 | url-status = dead | archive-date = August 5, 2023 }}</ref><ref name="NicholsGlennon1984">{{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 }}</ref>

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

==Pharmacology== ===Pharmacodynamics=== DOIB is a full agonist of the serotonin 5-HT2A receptor, with an {{Abbrlink|EC50|half-maximal effective concentration}} of 12.6{{nbsp}}nM and an {{Abbrlink|Emax|maximal efficacy}} of 98.8%, both for calcium mobilization.<ref name="FlanaganBillacLandry2021" /> It is about one-third as potent as DOM in rodent drug discrimination tests and also substitutes for LSD in these tests.<ref name="PiHKAL" /><ref name="OberlenderKothariNichols1984">{{cite journal | vauthors = Oberlender RA, Kothari PJ, Nichols DE, Zabik JE | title = 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 | journal = J Med Chem | volume = 27 | issue = 6 | pages = 788–792 | date = June 1984 | pmid = 6737421 | doi = 10.1021/jm00372a015 | url = https://chemistry.mdma.ch/hiveboard/rhodium/pdf/nichols/nichols-branched.4-substituents.pdf }}</ref><ref name="Nichols2012" /><ref name="Nichols2018" /> In addition to its psychedelic effects, DOIB has highly potent anti-inflammatory effects in preclinical research.<ref name="FlanaganBillacLandry2021">{{cite journal | vauthors = Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD | title = Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore | journal = ACS Pharmacol Transl Sci | volume = 4 | issue = 2 | pages = 488–502 | date = April 2021 | pmid = 33860179 | pmc = 8033619 | doi = 10.1021/acsptsci.0c00063 | url = https://www.researchgate.net/publication/360537036 | quote = 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), [...]}}</ref> It was more potent than almost any other tested psychedelic.<ref name="FlanaganBillacLandry2021" /> The drug was notably more potent than (''R'')-DOI, but was less potent than 2C-I (the most potent assessed compound).<ref name="FlanaganBillacLandry2021" />

==Chemistry== ===Synthesis=== The chemical synthesis of DOIB has been described.<ref name="PiHKAL" />

===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.<ref name="PiHKAL" /><ref name="ShulginManningDaley2011" />

Some other notable analogues of DOIB include DOBU (''n''-butyl), DOSB (''sec''-butyl), and DOTB (''tert''-butyl).<ref name="Nichols2012" /><ref name="Nichols2018" /><ref name="Shulgin2003" /><ref name="JacobShulgin1994" /><ref name="NicholsGlennon1984" />

==Society and culture== ===Legal status=== ====Canada==== DOIB is a controlled substance in Canada under phenethylamine blanket-ban language.<ref name="CDSA">{{cite web | title=Controlled Drugs and Substances Act | website=Department of Justice Canada | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html | access-date=19 January 2026}}</ref>

==References== {{Reflist}}

==External links== * [https://isomerdesign.com/pihkal/explore/235 DOIB - Isomer Design]

Category:5-HT2A agonists Category:Anti-inflammatory agents Category:DOx (psychedelics) Category:Isobutyl compounds Category:Psychedelic phenethylamines Category:Serotonin receptor agonists