2,5-Dimethoxy-4-propylamphetamine

Last updated
DOPR
DOPR chemical structure.svg
DOPR-3d-sticks.png
Clinical data
Other names2,5-Dimethoxy-4-propylamphetamine; 4-Propyl-2,5-dimethoxyamphetamine; DOPR; DOPr
Routes of
administration 		Oral [1]
Drug class Serotonin receptor agonist; Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Onset of action Very slow [1]
Duration of action 20–30 hours [1]
Identifiers
  • 1-(2,5-dimethoxy-4-propylphenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C14H23NO2
Molar mass 237.343 g·mol−1
3D model (JSmol)
  • CCCC1=CC(=C(C=C1OC)CC(C)N)OC
  • InChI=1S/C15H25NO2/c1-5-6-11-8-14(17-4)12(7-10(2)15)9-13(11)16-3/h8-10H,5-7,15H2,1-4H3 X mark.svgN
  • Key:UEEAUFJYLUJWQJ-UHFFFAOYSA-N Yes check.svgY
   (verify)

2,5-Dimethoxy-4-propylamphetamine (DOPR) is a psychedelic drug of the phenethylamine, amphetamine, and DOx families related to DOM. [1] [2] It is the derivative of DOM in which the methyl group at the 4 position has been replaced with a propyl group. [1] The drug is taken orally. [1]

Contents

The drug acts as a serotonin receptor agonist, including of the serotonin 5-HT2A receptor. [2] [3] It produces psychedelic-like effects in animals. [2] [3]

DOPR was first described in the literature by Alexander Shulgin in 1970. [4] Subsequently, it was described in greater detail by Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). [1]

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists DOPR's dose as 2.5 to 5 mg orally and its duration as 20 to 30 hours. [1] It is said to have a very slow onset. [1] The effects of DOPR have been reported to include closed-eye imagery, visuals, thinking changes, and insomnia and sleep disruption, among others. [1] In one of the reports, it was described as a "heavy duty psychedelic", including strong and unignorable visuals. [1]

Interactions

Pharmacology

Pharmacodynamics

DOPR acts as an agonist of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. [2] [5] [6] [3] [7] It has very weak affinity for the serotonin 5-HT1 receptor. [8] The drug has also been assessed at other receptors. [2]

It produces the head-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents. [2] [3] It is slightly more potent but slightly less efficacious than DOM in producing the head-twitch response. [2] As with many other psychedelics, DOPR shows an inverted U-shaped dose–response curve in terms of the HTR, increasing it at lower doses and having diminished effectiveness at higher doses. [2] [3]

DOPR showed no significant effects on locomotor activity in rodents at the assessed doses, but showed a trend towards hyperlocomotion at the highest dose. [3] In a subsequent study however, it produced hyperlocomotion at lower doses and hypolocomotion at higher doses. [2] The drug has shown pro-motivational effects in rodents at sub-hallucinogenic doses or so-called "microdoses". [5] [6] [9] DOPR's close analogue DOET has also been clinically studied at sub-hallucinogenic doses as a "psychic energizer". [10] [11] [12] [13] [14] [15] DOPR produces antidepressant-like effects in rodents. [9]

At higher doses, DOPR produces hypothermia in rodents. [2]

Pharmacokinetics

DOPR crosses the blood–brain barrier in rodents. [2] The drug showed the highest brain/plasma ratio among DOM homologues in rodents, whereas 2,5-dimethoxyamphetamine (2,5-DMA) showed the lowest. [2] This was involved in potency differences between the drugs. [2]

Chemistry

Synthesis

The chemical synthesis of DOPR has been described. [1]

Analogues

Analogues of DOPR include DOM, DOET, DOiP, DOBU, DOAM, DOPF, 2C-P, and 4C-P, among others. [1]

History

DOPR was first described in the literature by Alexander Shulgin in 1970. [4] Subsequently, it was described in greater detail by Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). [1]

Society and culture

Canada

DOPR is a controlled substance in Canada under phenethylamine blanket-ban language. [16]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. United States: Transform Press. p. 978. ISBN   0-9630096-0-5.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 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 (November 2025). "The 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effects" (PDF). Mol Psychiatry. doi:10.1038/s41380-025-03325-1. PMID   41193673.
  3. 1 2 3 4 5 6 Cunningham MJ, Bock HA, Serrano IC, Bechand B, Vidyadhara DJ, Bonniwell EM, Lankri D, Duggan P, Nazarova AL, Cao AB, Calkins MM, Khirsariya P, Hwu C, Katritch V, Chandra SS, McCorvy JD, Sames D (January 2023). "Pharmacological Mechanism of the Non-hallucinogenic 5-HT2A Agonist Ariadne and Analogs". ACS Chemical Neuroscience. 14 (1): 119–135. doi:10.1021/acschemneuro.2c00597. PMC   10147382 . PMID   36521179. We propose the following rationale for the rapid effects of Ariadne in the mouse [Parkinson's disease (PD)] model, as an initial guiding hypothesis for future studies. The in vitro profile suggests that Ariadne's effect on dopamine neurotransmission is indirect, namely not via direct modulation of DAT or dopamine receptors. It has been demonstrated that 5-HT2A agonists increase dopamine release in nucleus accumbens and other regions of the mesolimbic system.43 It is therefore likely that 5-HT2A agonists also stimulate DA release in more dorsal areas of the striatum that are compromised by the PD pathology.
  4. 1 2 "phenethylamines and their pharmacologically-acceptable salts". Google Patents. 14 July 1969. Retrieved 27 November 2025.
  5. 1 2 Noback M, Kenton JA, Klein AK, Hughes ZA, Kruegel AC, Schmid Y, Halberstadt AL, Young JW (February 2025). "Low (micro)doses of 2,5-dimethoxy-4-propylamphetamine (DOPR) increase effortful motivation in low-performing mice". Neuropharmacology. 268 110334. doi: 10.1016/j.neuropharm.2025.110334 . PMID   39900138. According to a recent publication (Cunningham et al., 2023), DOPR acts as a potent agonist at the 5-HT2A receptor when tested in BRET assays of Gq dissociation (EC50 = 1.7 nM, Emax = 98.9% relative to 5-HT) and β-arrestin2 recruitment (EC50 = 7.96 nM, Emax = 99.8% relative to 5-HT).
  6. 1 2 Noback M, Kenton J, Klein A, Hughes Z, Kruegel A, Young J (December 2022). "ACNP 61st Annual Meeting: Poster Abstracts P541 - P809: P572. 2,5-Dimethoxy-4-Propylamphetamine (DOPR) Increased Effortful Motivation in Mice". Neuropsychopharmacology. 47 (Suppl 1): 371–520 (390–390). doi:10.1038/s41386-022-01486-z. PMC   9714408 . PMID   36456695. DOPR caused a dose-dependent increase in HTR (F(5,30)=60.0, p < 0.0001), with doses of 3.2 and 10 mg/kg passing a Bonferroni post hoc correction relative to vehicle (p < 0.002), and peak effect at 3.2 mg/kg. [...] The binding affinity at 5-HT2A of the two compounds was similar, with DOPR having a Ki of 17.56 nM and DOI having a Ki of 14.51 nM. [...] DOPR and DOI also show agonist activity at 5-HT2A (EC50 of 0.12 and 0.19 nM, respectively) and 5-HT2C (EC50 of 0.27 and 0.82 nM, respectively) receptors, with >25-fold lower potency at 5-HT2B receptors and no significant activity at 5-HT1A (both > 1,000 nM EC50). [...] The positive effect of DOPR on effortful motivation points to possible therapeutic applications in psychiatric illness states characterized by reduced effortful motivation as measured by the PRBT. The similarity of effects of DOPR to well-studied drugs such as DOI and amphetamine provides a useful reference point to interpret its pharmacological effects. Importantly, the doses needed to increase breakpoint in the PRBT were as low as 0.0106 mg/kg. While 0.1 mg/kg increased HTR, this effect was not significant, and maximal effect at 3.2 mg/kg, supporting the premise that low doses of DOPR may be therapeutic in anhedonia states without causing unwanted hallucinogenic side effects.
  7. ↑ Hemanth P, Nistala P, Nguyen VT, Eltit JM, Glennon RA, Dukat M (2023). "Binding and functional structure-activity similarities of 4-substituted 2,5-dimethoxyphenyl isopropylamine analogues at 5-HT2A and 5-HT2B serotonin receptors". Frontiers in Pharmacology. 14 1101290. doi: 10.3389/fphar.2023.1101290 . PMC   9902381 . PMID   36762110.
  8. ↑ Glennon RA (January 1987). "Central serotonin receptors as targets for drug research". J Med Chem. 30 (1): 1–12. doi:10.1021/jm00384a001. PMID   3543362. Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites
  9. 1 2 Noback M, Flesher M, Cuccurazzu B, Halberstadt A, Young J (2026). "ACNP 64th Annual Meeting: Poster Abstracts P584-P872: The psychedelic DOPR improves depression-related behavior in mice". Neuropsychopharmacology. 51 (S1): 410–571. doi:10.1038/s41386-025-02281-2. ISSN   0893-133X. PMC   12783840 . PMID   41507446 . Retrieved 18 January 2026.
  10. ↑ Baggott MJ (1 October 2023). "Learning about STP: A Forgotten Psychedelic from the Summer of Love" (PDF). History of Pharmacy and Pharmaceuticals. 65 (1): 93–116. doi: 10.3368/hopp.65.1.93 . ISSN   2694-3034 . Retrieved 26 January 2025.
  11. ↑ Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN   978-1-4757-0512-6.
  12. ↑ Snyder SH, Faillace LA, Weingartner H (September 1968). "DOM (STP), a new hallucinogenic drug, and DOET: effects in normal subjects". Am J Psychiatry. 125 (3): 113–120. doi:10.1176/ajp.125.3.357. PMID   4385937.
  13. ↑ Snyder SH, Faillace LA, Weingartner H (July 1969). "A new psychotropic agent. Psychological and physiological effects of 2,5-dimethoxy-4-ethyl amphetamine (DOET) in man". Arch Gen Psychiatry. 21 (1): 95–101. doi:10.1001/archpsyc.1969.01740190097014. PMID   4389442.
  14. ↑ Snyder SH, Weingartner H, Faillace LA (January 1971). "DOET (2,5-dimethoxy-4-ethylamphetamine), a new psychotropic drug. Effects of varying doses in man". Arch Gen Psychiatry. 24 (1): 50–55. doi:10.1001/archpsyc.1971.01750070052006. PMID   4923215.
  15. ↑ Snyder SH, Unger S, Blatchley R, Barfknecht CF (July 1974). "Stereospecific actions of DOET (2,5-dimethoxy-4-ethylamphetamine) in man". Arch Gen Psychiatry. 31 (1): 103–106. doi:10.1001/archpsyc.1974.01760130079013. PMID   4599412.
  16. ↑ "Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.
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