2,5-Dimethoxy-4-amylamphetamine

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists the dose of DOAM as 10mg orally and its duration as unknown. DOAM was reported to produce a bare threshold and tenseness. In other publications however, DOAM has been said to produce threshold effects at 5 to 10mg orally and to be hallucinogenic at a dose of 40mg, with about 10-fold higher potency than mescaline. In any case, it shows far lower psychedelic potency than other DOx drugs such as DOM. No qualitative description of its effects at hallucinogenic doses is available.

Interactions

Pharmacology

Pharmacodynamics

DOAM has been found to be a moderate- to high-efficacy partial agonist of the serotonin 5-HT2A receptor. 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. The drug is a full agonist of the serotonin 5-HT2B and 5-HT2C receptors. 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. DOAM shows very low potency as a human trace amine-associated receptor 1 (TAAR1) agonist. It does not bind to the monoamine transporters. Other receptor interactions have also been described.

The drug produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. However, it produces only a weak head-twitch response and is less potent and much less efficacious than DOM in this regard. 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. It was also unable to antagonize the DOM stimulus at the assessed doses, and behavioral disruption at higher doses prevented further assessment. Other effects of DOAM in rodents include hyperlocomotion at lower doses, hypolocomotion at higher doses, and hypothermia at higher doses.

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.

Pharmacokinetics

DOAM crosses the blood–brain barrier in rodents.

Chemistry

Synthesis

The chemical synthesis of DOAM has been described.

Analogues

Analogues of DOAM include 2,5-dimethoxyamphetamine (2,5-DMA), DOM, DOET, DOPR, DOBU, and DOHx, among others.

History

DOAM was first described in the scientific literature by Alexander Shulgin and colleagues in 1975. Subsequently, it was described in greater detail by Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).

Society and culture

Legal status

Canada

DOAM is a controlled substance in Canada under phenethylamine blanket-ban language.

References

References

1. {{CitePiHKAL
2. (November 2025). "The 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effects". Mol Psychiatry.
3. (1978). "Mescaline analogs: substitutions at the 4-position". NIDA Res Monogr.
4. (December 1975). "Psychotomimetic phenylisopropylamines. 5. 4-Alkyl-2,5-dimethoxyphenylisopropylamines". J Med Chem.
5. Shulgin, Alexander T.. (1978). "Stimulants". Springer US.
6. (2022). "Monoamine Receptor and Transporter Interaction Profiles of 4-Alkyl-Substituted 2,5-Dimethoxyamphetamines". The FASEB Journal.
7. (April 1982). "A comparison of the behavioral effects of DOM homologs". Pharmacol Biochem Behav.
8. (1989). "Stimulus properties of hallucinogenic phenalkylamines and related designer drugs: formulation of structure-activity relationships". NIDA Res Monogr.
9. (14 November 1989). "Probing Bioactive Mechanisms". American Chemical Society.
10. (March 1990). "A structure-affinity study of the binding of 4-substituted analogues of 1-(2,5-dimethoxyphenyl)-2-aminopropane at 5-HT2 serotonin receptors". Journal of Medicinal Chemistry.
11. (August 2000). "1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists". Journal of Medicinal Chemistry.
12. 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
13. "Controlled Drugs and Substances Act".