2,5-Dimethoxy-4-propylamphetamine (DOPR) is apsychedelicdrug of thephenethylamine,amphetamine, andDOx families.[1] It was firstsynthesized byAlexander Shulgin, and was described in his bookPiHKAL (Phenethylamines i Have Known And Loved).[1] Very little data exists about the pharmacological properties, metabolism, and toxicity of DOPR.
According toAlexander Shulgin inPiHKAL, thedosage of DOPR is 2.5 to 5mg and itsduration is 20 to 30hours.[1] He described DOPR as a "heavy duty psychedelic", complete with alterations of the thought process and visual distortion.[1]
It produces thehead-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents.[4] As with many other psychedelics, DOPR shows aninverted U-shapeddose–response curve in terms of the HTR, increasing it at lower doses and having diminished effectiveness at higher doses.[4]
The alternativestructural isomerDOIP, with a 4-isopropyl substitution, is also known but is around ten times weaker than DOPR, with an active dose of some 20–30 mg (as compared to 2–5 mg for DOPR).[1]
^abNoback 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.PMC9714408.PMID36456695.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.
^abcdCunningham 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.PMC10147382.PMID36521179.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.
^Glennon RA (January 1987). "Central serotonin receptors as targets for drug research".J Med Chem.30 (1):1–12.doi:10.1021/jm00384a001.PMID3543362.Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites
^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.PMID4385937.
^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.PMID4389442.
^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.PMID4923215.
^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.PMID4599412.
