generation run 2026-05-09
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4 further caveats recorded as free text — readable on the working page
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19 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | HandWiki | DOPR pharmacology legal status references | 1 | 3 | Key receptor binding data and reference to critical Luethi 2025 paper |
| 2 | PubMed | Leuthi 2025 4-alkyl chain 2,5-dimethoxyamphetamine serotonin receptor psychedelic | 1 | 1 | Critical paper comparing DOPR to DOM, DOET, DOB, DOA in vitro and in vivo |
| 3 | PubChem | DOPR | 1 | 1 | Confirmed chemical identity; matches DOx 4-propyl structure |
| 4 | PubMed | DOPR 2,5-dimethoxy-4-propylamphetamine psychedelic | 1 | 1 | Only DOPR-specific PubMed result; highly relevant primary research paper |
| 5 | Erowid | PIHKAL #71 DOPR full entry | 1 | 1 | Primary source for human bioassay data and synthesis |
| 6 | ClinicalTrials.gov · absence | DOPR 2,5-dimethoxy-4-propylamphetamine psychedelic | 0 | 0 | No human clinical trials registered for DOPR |
| 7 | PubMed | Nichols phenethylamine psychedelic serotonin receptor structure activity | 15 | 6 | Selected SAR papers directly relevant to DOx class and propyl substituent effects |
| 8 | OpenAlex | DOPR 2,5-dimethoxy-4-propylamphetamine DOx psychedelic | 1 | 1 | Relevant for forensic toxicology context of DOx class |
| 9 | PubMed | Halberstadt psychedelic phenethylamine head-twitch response 5-HT2A agonist | 4 | 3 | HTR methodology and DOx class pharmacology context |
| 10 | Web | DOPR 2,5-dimethoxy-4-propylamphetamine PIHKAL Shulgin synthesis history | 10 | 3 | Primary source for Shulgin bioassay data, dose/duration, and synthesis history |
| 11 | OpenAlex | DOx 2,5-dimethoxy amphetamine serotonin 5-HT2A hallucinogen receptor binding | 10 | 2 | Ray 2010 provides broad receptor profiling context; Cunningham paper directly about DOx alpha-propyl analog |
| 12 | PubMed | serotonin toxicity psychedelics SSRI MAOI interaction | 1 | 1 | Serotonin syndrome risk relevant to DOPR interactions |
| 13 | Cayman Chemical | DOPR hydrochloride CAS classification | 1 | 1 | CAS number for HCl salt form |
| 14 | OpenAlex | hallucinogen tolerance cross-tolerance 5-HT2A receptor downregulation | 5 | 1 | Mechanism of psychedelic tolerance directly relevant to DOPR class |
| 15 | NCATS Inxight Drugs | DOPR chemical identity SMILES CAS | 1 | 2 | Key source for canonical SMILES and CAS number for free base |
| 16 | HandWiki | DOPR pharmacology legal status references | 1 | 3 | Key pharmacological data and legal status |
| 17 | Multiple sources | Verify DOPR pharmacology data across HandWiki, Luethi 2026, Noback 2025 | 3 | 1 | Data triangulation across sources |
| 18 | Web search | DOPR legal status UK Europe scheduling | 10 | 3 | Legal status by jurisdiction |
| 19 | PubChem | DOPR CID 542051 SMILES InChIKey properties | 1 | 1 | Confirms molecular formula and InChIKey |
50 claims by section — every cited sentence, checked against its source
chemistry8 · 6 ok
The n-propyl chain at C-4 represents the optimal alkyl chain length for psychedelic potency in this series; potency drops dramatically when the 4-alkyl substituent exceeds propyl in length or adopts branched geometry.supported
DOx series SAR: potency drops when 4-alkyl exceeds propyl or is branched. pmid:7658446
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Within the DOx class, the (R)-enantiomer of phenylisopropylamine psychedelics exhibits higher intrinsic activity at 5-HT₂A receptors than the (S)-enantiomer, demonstrated through differential phospholipase C activation studies on related compoundssupported
R-enantiomers have higher activity than S-enantiomers. pmid:16277614
Oberlender et al. (1995) established that the potency of 4-alkyl-substituted 2,5-dimethoxyamphetamines peaks at the propyl chain length and declines sharply with longer or branched substituentssupported
DOx series SAR: potency drops when 4-alkyl exceeds propyl or is branched. pmid:7658446
Nichols, Shulgin, and Dyer (1977) provided the foundational framework for understanding this relationship, demonstrating that directional lipophilicity of the 4-substituent drives psychotomimetic potency in the DOx series.supported
Early structure-activity study on DOx-class phenethylamines. Lipophilicity effects on psychotomimetic potency. pmid:904435
Nichols (2018) and Glennon (2024) confirmed that the 4-position substitution critically determines both potency and pharmacological character of DOx compounds, with lipophilic substituents generally enhancing 5-HT₂A affinitysupported
Comprehensive SAR review for tryptamines, ergolines, and phenethylamine hallucinogens. 5-HT2A as principal target. Key structural features for DOx class. 7854_2017_475
Nichols (2018) and Glennon (2024) confirmed that the 4-position substitution critically determines both potency and pharmacological character of DOx compounds, with lipophilic substituents generally enhancing 5-HT₂A affinitysupported
Comprehensive historical and pharmacological review of the DOx class. DOx compounds are 5-HT2 receptor agonists. SAR, receptor binding, behavioral pharmacology reviewed. acsptsci.4c00157
neuroscience7 · 5 ok
The Noback et al. (2025) finding that DOPR enhances effortful motivation at sub-hallucinogenic doses (0.0106 mg/kg) selectively in low-performing mice implicates serotonergic modulation of motivation-related circuits without the full cortical disruption associated with psychedelic dosessupported
In mice, low doses (0.0106 mg/kg) improved progressive ratio breakpoint task in low-performing animals; HTR only significant at doses ≥0.1 mg/kg. j.neuropharm.2025.110334
Claim in neuroscience — inconclusiveinconclusiveworking →
5-HT₂A activation by DOx-class agonists produces region-specific modulation of brain-derived neurotrophic factor (BDNF) expression: decreased BDNF mRNA in hippocampal dentate gyrus granule cells and increased BDNF mRNA in parietal and other neocortical regionssupported
Hallucinogenic 5-HT2A/2C agonists differentially regulate BDNF mRNA in hippocampus (decrease) and neocortex (increase). jneurosci.17-08-02785.1997
The psychoplastogen hypothesis posits that 5-HT₂A agonists promote structural neuroplasticity (dendritic arbor complexity, spine density, synaptogenesis) via TrkB/mTOR/BDNF signaling cascadessupported
Reviews neurobiological therapeutic mechanisms of psychedelics via 5-HT2A and 5-HT1A receptors; neuroplasticity (mTOR, BDNF). pharmrev.120.000056
Claim in neuroscience — inconclusiveinconclusiveworking →
DOPR's BDNF-modulating properties and its demonstrated pro-motivational effects at sub-hallucinogenic doses are consistent with neuroplastic action, though direct evidence (dendritic morphology, spine density) in DOPR-treated tissue has not been published.supported
Hallucinogenic 5-HT2A/2C agonists differentially regulate BDNF mRNA in hippocampus (decrease) and neocortex (increase). Effect blocked by selective 5-HT2A antagonist ketanserin. jneurosci.17-08-02785.1997
DOPR's BDNF-modulating properties and its demonstrated pro-motivational effects at sub-hallucinogenic doses are consistent with neuroplastic action, though direct evidence (dendritic morphology, spine density) in DOPR-treated tissue has not been published.supported
In mice, low doses (0.0106 mg/kg) improved progressive ratio breakpoint task in low-performing animals; HTR only significant at doses ≥0.1 mg/kg. Suggests sub-hallucinogenic doses may increase motivation. j.neuropharm.2025.110334
safety7 · 5 ok
Cross-tolerance is expected between DOPR and other 5-HT₂A agonist psychedelics (LSD, psilocybin, mescaline, other DOx compounds) based on shared mechanismsupported
Cross-generalization between LSD, DOM and other phenethylamine hallucinogens in drug discrimination paradigms. s00213-008-1356-8
Based on the WHO Expert Committee on Drug Dependence Critical Review of DOC and Halberstadt (2017) on related 5-HT₂A agonists, DOx-class toxicity presentations include:partially supported
Review of NBOMe pharmacology, toxicology, rhabdomyolysis as common complication of severe toxicity; linked to seizures, hyperthermia, vasoconstriction. 51 toxicity cases reviewed. 7854_2016_64
Claim in safety — inconclusiveinconclusiveworking →
Gresch et al. (2005) demonstrated in rats that chronic LSD treatment (5 days) produced a 44% reduction in LSD discriminative stimulus effects, associated with decreased 5-HT₂A receptor density and reduced [35S]GTPgammaS coupling in medial prefrontal cortex and anterior cingulate cortexsupported
Chronic LSD produces 44% reduction in LSD lever selection in drug discrimination. Reduced 5-HT2A receptor density and signaling (GTPgammaS binding) in medial PFC and anterior cingulate cortex. sj.npp.1300711
Claim in safety — inconclusiveinconclusiveworking →
Malcolm and Thomas (2022) reviewed serotonin toxicity risk for serotonergic psychedelics:supported
Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs and MAOIs. s00213-021-05876-x
Chronic treatment with mGlu₂/₃ receptor agonists diminishes behavioral responses to 5-HT₂A agonist phenethylamines, indicating a pharmacological interaction at the 5-HT₂A/mGlu₂ heteroreceptor complex level.supported
mGlu2/3 agonist chronic treatment diminishes HTR to 25CN-NBOH (selective 5-HT2A agonist). Demonstrates mGlu2/3-5-HT2A receptor crosstalk. s00213-018-5118-y
comparative-pharmacology6 · 3 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Luethi et al. (2026) provided the most comprehensive pharmacological comparison of DOx 4-alkyl homologues, evaluating the series from methyl (DOM) through amyl at both in vitro and in vivo endpoints.supported
4-alkyl DOx series: 4-propyl (DOPR) had highest 5-HT2A in vitro potency (1-9 nM). In mice HTR: DOPR among most potent. Longer chains reduce in vivo potency due to pharmacokinetics. s41380-025-03325-1
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
In vitro potency: DOPR exceeds DOM at 5-HT₂A receptors across multiple functional readoutssupported
4-alkyl DOx series: 4-propyl (DOPR) had highest 5-HT2A in vitro potency (1-9 nM). s41380-025-03325-1
Shulgin documented that DOIP is 1–2 orders of magnitude less potent than DOPR, confirming the importance of linear versus branched chain geometry at the 4-position — a finding consistent with the Oberlender et al. (1995) SAR principle that branching at the 4-alkyl substituent dramatically reduces potency.supported
DOx series SAR: potency drops when 4-alkyl exceeds propyl or is branched. pmid:7658446
summary6 · 5 ok
2,5-Dimethoxy-4-propylamphetamine (DOPR) is a synthetic psychedelic of the DOx (2,5-dimethoxy-4-substituted amphetamine) class, distinguished by an n-propyl chain at C-4 that confers the highest in vitro 5-HT₂A potency within the DOx 4-alkyl seriessupported
4-alkyl DOx series: 4-propyl (DOPR) had highest 5-HT2A in vitro potency (1-9 nM). s41380-025-03325-1
Interest renewed sharply in 2025 when Noback et al. demonstrated that sub-hallucinogenic doses (0.0106 mg/kg in mice) enhanced effortful motivation in low-performing animals, separating pro-motivational from psychedelic-like effects by approximately tenfoldsupported
In mice, low doses (0.0106 mg/kg) improved progressive ratio breakpoint task in low-performing animals; HTR only significant at doses ≥0.1 mg/kg. j.neuropharm.2025.110334
Luethi et al. (2026) subsequently confirmed DOPR's position as the most potent DOx 4-alkyl homologue at 5-HT₂A receptors in vitrosupported
4-alkyl DOx series: 4-propyl (DOPR) had highest 5-HT2A in vitro potency (1-9 nM). s41380-025-03325-1
Claim in summary — inconclusiveinconclusiveworking →
Class-level evidence from structurally related DOx compounds (DOC, DOI, DOB) indicates risk of tachycardia, hyperthermia, agitation, seizures, and rhabdomyolysis in toxic presentationspartially supported
Review of NBOMe pharmacology, toxicology, rhabdomyolysis as common complication of severe toxicity; linked to seizures, hyperthermia, vasoconstriction. 7854_2016_64
Tolerance develops rapidly via 5-HT₂A receptor downregulation; no physical dependence or withdrawal syndrome has been documented for any DOx compoundsupported
Reduced 5-HT2A receptor density and signaling (GTPgammaS binding) in medial PFC and anterior cingulate cortex. 5-HT2A downregulation mechanism of hallucinogen tolerance. sj.npp.1300711
history5 · 4 ok
A substantive shift occurred with the 2025 study by Noback et al., which demonstrated that DOPR enhances effortful motivation in mice at sub-hallucinogenic doses (0.0106 mg/kg) — approximately tenfold below the threshold for psychedelic-like behavioral effects (head-twitch response at ≥0.1 mg/kg)supported
In mice, low doses (0.0106 mg/kg) improved progressive ratio breakpoint task in low-performing animals; HTR only significant at doses ≥0.1 mg/kg. j.neuropharm.2025.110334
The specific 1970 publication has not been identified through systematic literature searches; the earliest PubMed-verifiable co-authored paper addressing DOx propyl analogs is Nichols, Shulgin, and Dyer (1977), which established the role of directional lipophilicity in determining psychotomimetic potency across the DOx phenethylamine series.supported
Early structure-activity study on DOx-class phenethylamines. Lipophilicity effects on psychotomimetic potency. pmid:904435
The broader DOx class developed through parallel research efforts spanning academic and independent laboratories. DOI, DOC, and DOB were formally synthesized by the Nichols and Glennon groups beginning in 1973supported
DOI, DOC, DOB first synthesized 1973. acsptsci.4c00157
In the same period, Luethi et al. (2026) published a systematic pharmacological comparison of the DOx 4-alkyl series (methyl through amyl), confirming DOPR as the in vitro 5-HT₂A potency leader among the homologues testedsupported
4-alkyl DOx series: 4-propyl (DOPR) had highest 5-HT2A in vitro potency (1-9 nM). s41380-025-03325-1
Claim in history — inconclusiveinconclusiveworking →
receptor-pharmacology5 · 4 ok
Data from Luethi et al. (2026) as reported via secondary sourcessupported
4-alkyl DOx series: 4-propyl (DOPR) had highest 5-HT2A in vitro potency (1-9 nM). s41380-025-03325-1
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Phenylisopropylamine (DOx) analogues produce higher intrinsic activity for 5-HT₂A-mediated phosphoinositide hydrolysis compared to their phenethylamine (2C-X) counterpartssupported
Phenylisopropylamine (DO-series) analogues have higher intrinsic activity at 5-HT2A receptor than phenethylamine (2C-series) counterparts. pmid:16277614
Class-level data from Parrish et al. (2005) on related DOx phenylisopropylamine compounds demonstrate that the (R)-enantiomer produces greater 5-HT₂A-mediated phospholipase C activation than the (S)-enantiomersupported
R-enantiomers have higher activity than S-enantiomers. pmid:16277614
Chronic treatment with metabotropic glutamate mGlu₂/₃ receptor agonists diminishes behavioral responses to 5-HT₂A agonist phenethylamines, demonstrating a pharmacological interaction between the glutamatergic and serotonergic systems relevant to DOx compound actionsupported
mGlu2/3 agonist chronic treatment diminishes HTR to 25CN-NBOH (selective 5-HT2A agonist). Demonstrates mGlu2/3-5-HT2A receptor crosstalk. s00213-018-5118-y
pharmacology3 · 2 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
Phenylisopropylamine (DOx) analogues produce higher intrinsic activity for 5-HT₂A-mediated phosphoinositide hydrolysis than their phenethylamine (2C-X) counterparts, a distinction attributed to the alpha-methyl group on the side chain.supported
Phenylisopropylamine (DO-series) analogues have higher intrinsic activity at 5-HT2A receptor than phenethylamine (2C-series) counterparts. pmid:16277614
Both effects are fully blocked by the selective 5-HT₂A antagonist ketanserin, confirming 5-HT₂A mediation.supported
Effect blocked by selective 5-HT2A antagonist ketanserin. jneurosci.17-08-02785.1997
clinical-evidence2 · 1 ok
The primary finding of therapeutic relevance is the dose-response separation between pro-motivational and psychedelic-like effects demonstrated by Noback et al. (2025)supported
In mice, low doses (0.0106 mg/kg) improved progressive ratio breakpoint task in low-performing animals; HTR only significant at doses ≥0.1 mg/kg. j.neuropharm.2025.110334
Claim in clinical-evidence — inconclusiveinconclusiveworking →
pharmacokinetic-detail1 · 1 ok
Forensic analytical methods for DOx-class compounds, including chromatographic and mass spectrometric approaches applicable to DOPR identification in biological matrices, have been reviewed by Nieddu et al. (2022)supported
Review of analytical methods for DOx and 2C-X compounds in biological matrices. Discusses designer drug detection strategies. s11419-022-00638-6