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| Other names | 2,5-Dimethoxy-4-propylamphetamine; 4-Propyl-2,5-dimethoxyamphetamine; DOPR; DOPr |
| Routes of administration | Oral[1] |
| Drug class | Serotonin receptor agonist;Serotonin5-HT2 receptoragonist;Serotonin 5-HT2A receptor agonist;Serotonergic psychedelic;Hallucinogen |
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| Onset of action | Very slow[1] |
| Duration of action | 20–30 hours[1] |
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| Formula | C14H23NO2 |
| Molar mass | 237.343 g·mol−1 |
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2,5-Dimethoxy-4-propylamphetamine (DOPR) is apsychedelic drug of thephenethylamine,amphetamine, andDOx families related toDOM.[1][2] It is thederivative of DOM in which themethyl group at the 4 position has been replaced with apropyl group.[1] The drug is takenorally.[1]
The drug acts as aserotonin receptor agonist, including of theserotonin5-HT2A receptor.[2][3] It produces psychedelic-like effects in animals.[2][3]
DOPR was first described in the literature byAlexander Shulgin in 1970.[4] Subsequently, it was described in greater detail by Shulgin in his 1991 bookPiHKAL (Phenethylamines I Have Known and Loved).[1]
In his bookPiHKAL (Phenethylamines I Have Known and Loved),Alexander Shulgin lists DOPR's dose as 2.5 to 5 mgorally and itsduration as 20 to 30 hours.[1] It is said to have a very slowonset.[1] The effects of DOPR have been reported to includeclosed-eyeimagery,visuals, thinking changes, andinsomnia andsleep disruption, among others.[1] In one of the reports, it was described as a "heavy duty psychedelic", including strong and unignorable visuals.[1]
DOPR acts as anagonist of theserotonin5-HT2 receptors, including of the serotonin5-HT2A,5-HT2B, and5-HT2C receptors.[2][5][6][3][7] It has very weakaffinity for the serotonin5-HT1 receptor.[8] The drug has also been assessed at other receptors.[2]
It produces thehead-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents.[2][3] It is slightly morepotent but slightly lessefficacious thanDOM in producing the head-twitch response.[2] 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.[2][3]
DOPR showed no significant effects onlocomotor activity in rodents at the assessed doses, but showed a trend towardshyperlocomotion 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 shownpro-motivational effects in rodents at sub-hallucinogenic doses or so-called "microdoses".[5][6][9] DOPR's closeanalogueDOET has also been clinically studied at sub-hallucinogenic doses as a "psychic energizer".[10][11][12][13][14][15] DOPR producesantidepressant-like effects in rodents.[9]
At higher doses, DOPR produceshypothermia in rodents.[2]
DOPR crosses theblood–brain barrier in rodents.[2] The drug showed the highestbrain/plasma ratio amongDOMhomologues in rodents, whereas2,5-dimethoxyamphetamine (2,5-DMA) showed the lowest.[2] This was involved inpotency differences between the drugs.[2]
Thechemical synthesis of DOPR has been described.[1]
Analogues of DOPR includeDOM,DOET,DOiP,DOBU,DOAM,DOPF,2C-P, and4C-P, among others.[1]
DOPR was first described in the literature byAlexander Shulgin in 1970.[4] Subsequently, it was described in greater detail by Shulgin in his 1991 bookPiHKAL (Phenethylamines I Have Known and Loved).[1]
DOPR is acontrolled substance inCanada under phenethylamine blanket-ban language.[16]
DOPR is not an explicitlycontrolled substance in theUnited States.[17] However, it could be considered a controlled substance under theFederal Analogue Act if intended for human consumption.
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.
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).
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.
Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites
