2,5-Dimethoxy-4-amylamphetamine

{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 477211551 | drug_name = DOAM | image = DOAM.svg | image_class = skin-invert-image | width = 250px | image2 = 2,5-Dimethoxy-4-amylamphetamine-3D-spacefill.png | image_class2 = bg-transparent | width2 = 200px

| legal_status =

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 63779-90-8 | CAS_supplemental = | PubChem = 12262512 | PubChemSubstance = | IUPHAR_ligand = | DrugBank = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 10440619 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = N80EWL36CB | KEGG = | ChEBI = | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 161416 | NIAID_ChemDB = | PDB_ligand = | synonyms = DOAM; 2,5-Dimethoxy-4-amylamphetamine; 4-Amyl-2,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-pentylamphetamine; 4-Pentyl-2,5-dimethoxyamphetamine

| IUPAC_name = 1-(2,5-dimethoxy-4-pentylphenyl)propan-2-amine | C=16 | H=27 | N=1 | O=2 | SMILES = CCCCCC1=CC(OC)=C(CC(C)N)C=C1OC | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C16H27NO2/c1-5-6-7-8-13-10-16(19-4)14(9-12(2)17)11-15(13)18-3/h10-12H,5-9,17H2,1-4H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VLJORLCVOAUUKM-UHFFFAOYSA-N }}

'''2,5-Dimethoxy-4-amylamphetamine''' ('''DOAM'''), also known as '''2,5-dimethoxy-4-pentylamphetamine''', is a psychedelic drug of the phenethylamine, amphetamine, and DOx families related to DOM.<ref name="PiHKAL">{{CitePiHKAL}}</ref><ref name="LuethiGlatfelterPottie2025">{{cite journal | vauthors = Luethi D, Glatfelter GC, Pottie E, Sellitti F, Maitland AD, Gonzalez NR, Kryszak LA, Jackson SN, Hoener MC, Stove CP, Liechti ME, Smieško M, Baumann MH, Simmler LD, Rudin D | title = The 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effects | journal = Mol Psychiatry | volume = | issue = | pages = | date = November 2025 | pmid = 41193673 | doi = 10.1038/s41380-025-03325-1 | url = https://www.nature.com/articles/s41380-025-03325-1.pdf}}</ref> It is the derivative of DOM in which the methyl group at the 4 position has been replaced with an amyl (pentyl) group.<ref name="PiHKAL" /><ref name="LuethiGlatfelterPottie2025" /> The drug is taken orally.<ref name="PiHKAL" />

It is a serotonin receptor agonist, including of the serotonin 5-HT2A receptor.<ref name="LuethiGlatfelterPottie2025" /> The drug produces weak and mixed psychedelic-like effects in animals.<ref name="LuethiGlatfelterPottie2025" /><ref name="GlennonYoungRosecrans1982" /><ref name="SeggelYousifLyon1990" /><ref name="Glennon1989" />

DOAM was first described in the scientific literature by Alexander Shulgin and colleagues in 1975.<ref name="ShulginDyer1975" /> Subsequently, it was described in greater detail by Shulgin in his 1991 book ''PiHKAL'' (''Phenethylamines I Have Known and Loved'').<ref name="PiHKAL" />

==Use and effects== In his book ''PiHKAL'' (''Phenethylamines I Have Known and Loved''), Alexander Shulgin lists the dose of DOAM as greater than 10{{nbsp}}mg orally and its duration as unknown.<ref name="PiHKAL" /> DOAM was reported to produce a bare threshold and tenseness.<ref name="PiHKAL" /> In other publications however, DOAM has been said to produce threshold effects at 5 to 10{{nbsp}}mg orally and to be hallucinogenic at a dose of 40{{nbsp}}mg orally, with about 10-fold higher potency than mescaline.<ref name="BraunBraunJacob1978">{{cite journal | vauthors = Braun U, Braun G, Jacob P, Nichols DE, Shulgin AT | title = Mescaline analogs: substitutions at the 4-position | journal = NIDA Res Monogr | volume = | issue = 22 | pages = 27–37 | date = 1978 | pmid = 101882 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph22.pdf#page=38 | archive-url = https://web.archive.org/web/20230805004421/https://archives.nida.nih.gov/sites/default/files/monograph22.pdf#page=38 | url-status = dead | archive-date = August 5, 2023 | quote = TABLE II RELATIVE POSTENCIES IN MAN OF DIMETHOXYPHENYLISOPROPYLAMINE PSYCHOTOMIMETICS WITH VARIOUS SUBSTITUENTS ON THE 4-POSITION [...] Name: DOBU. Potency (total dose mg/man): 10 mg (e). Name: DOTB. Potency (total dose mg/man): >25 mg (d,f). Name: DOAM. Potency (total dose mg/man): 40 mg (e). [...] REFERENCES FOR TABLE II: [...] d. Shulgin, A.T., and Nichols, D.E. In: Stillman, R., and Willette, R. eds. Psychopharmacology of Hallucinogens. New York: Pergamon Press, 1978. e. Shulgin, A.T., and Dyer, D.C. J Med Chem, 18:1201, 1975. f. A > symbol indicates the absence of any activity at the stated dosage.}}</ref><ref name="Shulgin1978" /><ref name="ShulginDyer1975">{{cite journal | vauthors = Shulgin AT, Dyer DC | title = Psychotomimetic phenylisopropylamines. 5. 4-Alkyl-2,5-dimethoxyphenylisopropylamines | journal = J Med Chem | volume = 18 | issue = 12 | pages = 1201–1204 | date = December 1975 | pmid = 1195275 | doi = 10.1021/jm00246a006 | url = https://bitnest.netfirms.com/external/10.1021/jm00246a006| url-access = subscription }}</ref> In any case, it shows far lower psychedelic potency than other DOx drugs such as DOM.<ref name="BraunBraunJacob1978" /><ref name="Shulgin1978">{{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=3.4.11. 2,5-Dimethoxy-4-amylphenylisopropylamine: The last member of this series of homologs is 2,5-dimethoxy-4-amylphenylisopropylamine (77, DOAM). As will be seen below, it has been studied both in behavioral tests and in biochemical systems, and in both it appears to be of substantially reduced potency compared with its two immediately lower homologs. Limited human evaluation has provided the same results. Threshold effects are noticed at levels of 5-10 mg orally, and the compound has a stated effective potency of only 10 times that of mescaline (Shulgin and Dyer, 1975). No qualitative description of its intoxication syndrome at effective levels can be made from the limited experimental data available. [...]}}</ref> No qualitative description of its effects at hallucinogenic doses is available.<ref name="Shulgin1978" /><ref name="PiHKAL" />

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

==Pharmacology== ===Pharmacodynamics=== DOAM has been found to be a moderate- to high-efficacy partial agonist of the serotonin 5-HT2A receptor.<ref name="LuethiGlatfelterPottie2025" /><ref name="LuethiRudinHoener2022">{{cite journal | vauthors = Luethi D, Rudin D, Hoener MC, Liechti ME | 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 | article-number=fasebj.2022.36.S1.R2691 | doi-access=free | url=https://www.researchgate.net/publication/360369275 }}</ref> It also shows lower affinity for the serotonin 5-HT2B and 5-HT2C receptors, whereas it has very low affinity for the serotonin 5-HT1A receptor.<ref name="LuethiGlatfelterPottie2025" /><ref name="LuethiRudinHoener2022" /> The drug is a full agonist of the serotonin 5-HT2B and 5-HT2C receptors.<ref name="LuethiGlatfelterPottie2025" /> It is most potent as a serotonin 5-HT2C receptor agonist, whereas it shows far lower potency as an agonist of the serotonin 5-HT2B receptor than as an agonist of the serotonin 5-HT2A and 5-HT2C receptors.<ref name="LuethiGlatfelterPottie2025" /> DOAM shows very low potency as a human trace amine-associated receptor 1 (TAAR1) agonist.<ref name="LuethiGlatfelterPottie2025" /><ref name="LuethiRudinHoener2022" /> It does not bind to the monoamine transporters.<ref name="LuethiGlatfelterPottie2025" /><ref name="LuethiRudinHoener2022" /> Other receptor interactions have also been described.<ref name="LuethiGlatfelterPottie2025" />

The drug produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.<ref name="LuethiGlatfelterPottie2025" /> However, it produces only a weak head-twitch response and is less potent and much less efficacious than DOM in this regard.<ref name="LuethiGlatfelterPottie2025" /> In addition, DOAM fails to substitute for DOM in rodent drug discrimination tests, producing up to 35% responding followed up behavioral disruption at higher doses.<ref name="GlennonYoungRosecrans1982">{{cite journal | vauthors = Glennon RA, Young R, Rosecrans JA | title = A comparison of the behavioral effects of DOM homologs | journal = Pharmacol Biochem Behav | volume = 16 | issue = 4 | pages = 557–559 | date = April 1982 | pmid = 7071089 | doi = 10.1016/0091-3057(82)90414-2 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=08722eb1322400803893f721407308f48f0404cd| url-access = subscription }}</ref><ref name="SeggelYousifLyon1990" /><ref name="Glennon1989">{{cite journal | vauthors = Glennon RA | title = Stimulus properties of hallucinogenic phenalkylamines and related designer drugs: formulation of structure-activity relationships | journal = NIDA Res Monogr | volume = 94 | issue = | pages = 43–67 | date = 1989 | pmid = 2575229 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph94.pdf#page=54| archive-url = https://web.archive.org/web/20230511144224/https://archives.nida.nih.gov/sites/default/files/monograph94.pdf#page=54| url-status = dead| archive-date = May 11, 2023}}</ref> It was also unable to antagonize the DOM stimulus at the assessed doses, and behavioral disruption at higher doses prevented further assessment.<ref name="GlennonSeggel1989">{{cite book | vauthors = Glennon RA, Seggel MR | chapter=Interaction of Phenylisopropylamines with Central 5-HT2 Receptors: Analysis by Quantitative Structure—Activity Relationships | title=Probing Bioactive Mechanisms | publisher=American Chemical Society | publication-place=Washington, DC | volume=413 | date=14 November 1989 | isbn=978-0-8412-1702-7 | doi=10.1021/bk-1989-0413.ch018 | pages=264–280 | url=https://bitnest.netfirms.com/external/10.1021/bk-1989-0413.ch018}}</ref> Other effects of DOAM in rodents include hyperlocomotion at lower doses, hypolocomotion at higher doses, and hypothermia at higher doses.<ref name="LuethiGlatfelterPottie2025" />

As the 4-alkyl chain length in DOx is increased from shorter homologues such as DOM, DOET and DOPR which are all potent hallucinogens, the serotonin 5-HT2 receptor binding affinity increases, rising to a maximum with DOHx before falling again with even longer chains. Compounds with sufficiently long chains, such as DOAM, or with bulky groups such as DOTB, have reduced or absent psychedelic-type effects in animals and/or humans, suggesting that they may have reduced agonistic activity at the serotonin 5-HT2A receptor.<ref name="LuethiGlatfelterPottie2025" /><ref name="ShulginDyer1975" /><ref name="SeggelYousifLyon1990">{{cite journal|author5-link=Bryan Roth |vauthors=Seggel MR, Yousif MY, Lyon RA, Titeler M, Roth BL, Suba EA, Glennon RA |title=A structure-affinity study of the binding of 4-substituted analogues of 1-(2,5-dimethoxyphenyl)-2-aminopropane at 5-HT2 serotonin receptors |journal=Journal of Medicinal Chemistry |volume=33 |issue=3 |pages=1032–6 |date=March 1990 |pmid=2308135 |doi= 10.1021/jm00165a023 | quote = For example, using rats trained to discriminate DOM from saline, ED,, values for stimulus generalization are significantly correlated with 5-HT2 affinity. However, some of the compounds included in the present study (e.g., In and Io) possess a high affinity for the 5-HT2 sites but do not result in stimulus generalization.}}</ref><ref name="DowdHerrick-DavisEgan">{{cite journal |vauthors=Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, Glennon RA |title=1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists |journal=Journal of Medicinal Chemistry |volume=43 |issue=16 |pages=3074–84 |date=August 2000 |pmid=10956215 |doi= 10.1021/jm9906062}}</ref><ref>Patentscope. [https://patentscope.wipo.int/search/docs2/pct/WO2022192781/pdf/01d7O926L7q3Rk0wxUvdL1obPqEEFaJZwDeupe0-TEA Kruegel AC. Phenalkylamines and Methods of Making and Using the Same. Patent WO 2022/192781]. Retrieved 2025-05-12</ref>

===Pharmacokinetics=== DOAM crosses the blood–brain barrier in rodents.<ref name="LuethiGlatfelterPottie2025" />

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

===Analogues=== Analogues of DOAM include 2,5-dimethoxyamphetamine (2,5-DMA), DOM, DOET, DOPR, DOBU, and DOHx, among others.<ref name="PiHKAL" /><ref name="LuethiGlatfelterPottie2025" />

==History== DOAM was first described in the scientific literature by Alexander Shulgin and colleagues in 1975.<ref name="ShulginDyer1975" /> Subsequently, it was described in greater detail by Shulgin in his 1991 book ''PiHKAL'' (''Phenethylamines I Have Known and Loved'').<ref name="PiHKAL" />

==Society and culture== ===Legal status=== ====Canada==== DOAM 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/61 DOAM - Isomer Design] * [http://www.erowid.org/library/books_online/pihkal/pihkal061.shtml DOAM - PiHKAL - Erowid] * [http://pihkal.info/read.php?domain=pk&id=61 DOAM - PiHKAL - Isomer Design] * [https://tripsitter.com/doam/ DOAM: What Do We Know About This Mysterious Psychedelic? - Tripsitter]

Category:5-HT2A agonists Category:5-HT2B agonists Category:5-HT2C agonists Category:DOx (psychedelics) Category:Pentyl compounds Category:PiHKAL Category:Psychedelic phenethylamines