2,5-Dimethoxy-4-isobutylamphetamine

Pharmaceutical compound From Wikipedia, the free encyclopedia

2,5-Dimethoxy-4-isobutylamphetamine (DOIB or DOiBu) is a serotonin 5-HT_2A receptor agonist, serotonergic psychedelic, and anti-inflammatory drug of the phenethylamine, amphetamine, and DOx families.^[1]^[2]^[3]^[4]^[5]

Other names2,5-Dimethoxy-4-isobutylamphetamine; 4-Isobutyl-2,5-dimethoxyamphetamine; DOIB; DOiBu; 2,5-Dimethoxy-4-(2-methylpropyl)amphetamine

Routes of
administrationOral

Drug classSerotonin 5-HT_2A receptor agonist; Serotonergic psychedelic; Hallucinogen; Anti-inflammatory drug

ATC code

None

Quick facts Clinical data, Other names ...

DOIB
Clinical data

Other names	2,5-Dimethoxy-4-isobutylamphetamine; 4-Isobutyl-2,5-dimethoxyamphetamine; DOIB; DOiBu; 2,5-Dimethoxy-4-(2-methylpropyl)amphetamine
Routes of administration	Oral
Drug class	Serotonin 5-HT_2A receptor agonist; Serotonergic psychedelic; Hallucinogen; Anti-inflammatory drug
ATC code	None
Identifiers
IUPAC name 1-[2,5-dimethoxy-4-(2-methylpropyl)phenyl]propan-2-amine
CAS Number	89556-64-9
PubChem CID	44374984
ChemSpider	23231800
ChEMBL	ChEMBL161299
Chemical and physical data
Formula	C₁₅H₂₅NO₂
Molar mass	251.370 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC(C)CC1=CC(=C(C=C1OC)CC(C)N)OC
InChI InChI=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 Key:ZLESHKOTWSWEGW-UHFFFAOYSA-N

Use and effects

DOIB is active at doses of 10 to 15 mg orally, and hence is about one-third as potent as DOM.^[2]^[3]^[6]^[7]^[8]

Interactions

Pharmacology

Pharmacodynamics

DOIB is a full agonist of the serotonin 5-HT_2A receptor, with an EC₅₀Tooltip half-maximal effective concentration of 12.6 nM and an E_maxTooltip maximal efficacy of 98.8%, both for calcium mobilization.^[5] It is about one-third as potent as DOM in rodent drug discrimination tests and also substitutes for LSD in these tests.^[3]^[9]^[1]^[2] In addition to its psychedelic effects, DOIB has highly potent anti-inflammatory effects in preclinical research.^[5] It was more potent than almost any other tested psychedelic.^[5] The drug was notably more potent than (R)-DOI, but was less potent than 2C-I (the most potent assessed compound).^[5]

Chemistry

Synthesis

The chemical synthesis of DOIB has been described.^[3]

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.^[3]^[4]

Some other notable analogues of DOIB include DOBU (n-butyl), DOSB (sec-butyl), and DOTB (tert-butyl).^[1]^[2]^[6]^[7]^[8]

DOIB, DOSB, and DOTB.^[1]^[2]^[6]^[7]^[8]

Society and culture

Legal status

Canada

DOIB is a controlled substance in Canada under phenethylamine blanket-ban language.^[10]

References

[1]
Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi:10.1002/wmts.42. ISSN 2190-460X. 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. [...]
[2]
Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. 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).
[3]
Shulgin AT, Shulgin A (1991). "#63 DOBU 2,5-DIMETHOXY-4-(n)-BUTYLAMPHETAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. ISBN 978-0-9630096-0-9. OCLC 25627628. 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.
[4]
Shulgin A, Manning T, Daley PF (2011). "#60. DOM". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley, CA: Transform Press. pp. 118–129. ISBN 978-0-9630096-3-0. OCLC 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).
[5]
Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "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. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179. 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), [...]
[6]
Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4. Retrieved 1 February 2025.
[7]
Jacob P, Shulgin AT (1994). "Structure-activity relationships of the classic hallucinogens and their analogs" (PDF). NIDA Res Monogr. 146: 74–91. PMID 8742795. Archived from the original (PDF) on August 5, 2023.
[8]
Nichols DE, Glennon RA (1984). "Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens". In Jacobs BL (ed.). Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives. New York: Raven Press. pp. 95–142. ISBN 978-0-89004-990-7. OCLC 10324237.
[9]
Oberlender RA, Kothari PJ, Nichols DE, Zabik JE (June 1984). "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" (PDF). J Med Chem. 27 (6): 788–792. doi:10.1021/jm00372a015. PMID 6737421.
[10]
"Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.