DOB

The sole source of human toxicity data is a single confirmed overdose case report.supported

GC-MS confirmed DOB in gastric and urine samples. First DOB documentation in Czech Republic. pmid:15979834

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

The mechanistically related compound Bromo-DragonFLY has been specifically associated with fatal arterial vasospasm and limb ischemiasupported

Pharmacological, chemical, toxicological overview of Bromo-DragonFLY (DOB-DFLY analog). Associated with acute intoxications and fatalities. pmid:21592070

DOB and other DOx compounds can be identified by UPLC-QTOF-MS with characteristic product ions at m/z 178.0994, 163.0754, 147.0804, and 135.0810supported

Common DOx fragment ions at m/z 178.0994, 163.0754, 147.0804, 135.0810. dta.2171

Claim in safety — inconclusiveinconclusiveworking →

As a potent 5-HT₂A agonist, DOB shares the class-wide psychological risks documented for serotonergic psychedelics: acute anxiety, panic, paranoia, disorganized thought, and transient psychotic symptoms, particularly at higher doses or in unprepared contextssupported

Comprehensive review: psychedelics are agonists or partial agonists at brain 5-HT2A receptors... Generally physiologically safe, no dependence. Reviews rodent models, neuroimaging, clinical research. pr.115.011478

Claim in safety — inconclusiveinconclusiveworking →

Chronic administration of SSRIs downregulates 5-HT₂A receptors and attenuates the subjective effects of serotonergic hallucinogens, producing functional cross-tolerance.supported

Chronic SSRI administration attenuates subjective LSD effects, likely via 5-HT2A receptor downregulation. 0893-133x(95)00145-4

Serotonergic psychedelics as a class are not considered habit-forming and do not produce compulsive use patterns or withdrawal syndromessupported

Generally physiologically safe, no dependence. pr.115.011478

Chronic SSRI/SNRI use downregulates 5-HT₂A receptors and may significantly attenuate or abolish DOB's psychedelic effectssupported

Chronic SSRI administration attenuates subjective LSD effects, likely via 5-HT2A receptor downregulation. 0893-133x(95)00145-4

Claim in safety — inconclusiveinconclusiveworking →

Seizure disorders: Convulsions documented in the fatal overdose case.supported

One died 6 days later (serum 19 ng/mL) of convulsions and metabolic acidosis. pmid:15979834

The racemate binds with Kᵢ = 0.79 nM at [³H]DOB-labeled central 5-HT₂ receptors, while the active R-(−) enantiomer achieves Kᵢ = 0.2 nM at 5-HT₂Asupported

DOB itself Ki = 0.79 nM at [3H]DOB-labeled central 5-HT2 serotonin receptors. pmid:3211969

The racemate binds with Kᵢ = 0.79 nM at [³H]DOB-labeled central 5-HT₂ receptors, while the active R-(−) enantiomer achieves Kᵢ = 0.2 nM at 5-HT₂Asupported

R(-)-DOB Ki = 0.2 nM at 5-HT2A. pmid:15537358

R-(−)-DOB functions as a partial agonist with approximately 50% efficacy relative to serotonin in a 5-HT₂A-mediated calcium mobilization assay.supported

R(-)-DOB behaved as partial agonist (~50% efficacy) in 5-HT2-mediated calcium mobilization assay. pmid:15537358

Structure-activity relationships for biased agonism at 5-HT₂A have been characterized across the phenylalkylamine classsupported

Biased agonism analysis of phenylalkylamine 5-HT2A agonists; DOB included; beta-arrestin2 vs miniGαq recruitment. acschemneuro.3c00267

The behavioral consequences of DOB's hallucinogenic action — validated by the mouse head-twitch response (HTR), the standard rodent proxy for serotonergic hallucinogen activity — are abolished by selective 5-HT₂A antagonists, confirming receptor-level mediation.supported

DOB ED50 = 0.75 μmol/kg in mouse head-twitch response (HTR) assay. HTR is 5-HT2A receptor-mediated. j.neuropharm.2018.10.037

In the chronic spinal dog behavioral model, DOB was classified as "predominantly LSD-like with some amphetamine-like activity," exhibiting cross-tolerance to lsd while retaining a partial amphetamine-like pharmacological signature.partially supported

DOB predominantly LSD-like with some amphetamine-like activity in chronic spinal dog model. pmid:272982

No published human pharmacokinetic data exist for DOB. All pharmacokinetic characterization derives from: (a) a single confirmed overdose case report, (b) structural analog inference from 2c-b metabolism data, and (c) self-report documentation.supported

Two men ingested DOB; one survived (serum 13 ng/mL), one died 6 days later (serum 19 ng/mL) of convulsions and metabolic acidosis. First DOB documentation in Czech Republic. pmid:15979834

No published human pharmacokinetic data exist for DOB. All pharmacokinetic characterization derives from: (a) a single confirmed overdose case report, (b) structural analog inference from 2c-b metabolism data, and (c) self-report documentation.supported

2C-B (alpha-desMe analog of DOB) metabolized by hepatocytes from 6 species. pmid:15590110

Claim in pharmacology — inconclusiveinconclusiveworking →

In the only published confirmed overdose, serum DOB concentrations on hospital admission were 13 ng/mL (non-fatal subject, 113 kg body weight) and 19 ng/mL (fatal subject, 65 kg), with unknown ingestion times.supported

One survived (serum 13 ng/mL), one died 6 days later (serum 19 ng/mL) of convulsions and metabolic acidosis. pmid:15979834

Metabolic pathway inference relies on hepatocyte studies of 2c-b (4-bromo-2,5-dimethoxyphenethylamine), the alpha-desmethyl analog of DOB:supported

2C-B (alpha-desMe analog of DOB) metabolized by hepatocytes from 6 species. pmid:15590110

The [³H]DOB radioligand labels 5-HT₂ receptors in an agonist high-affinity state, yielding 10–100-fold higher affinities for agonist compounds compared to the antagonist radioligand [³H]ketanserinsupported

[3H]DOB as a radioligand gave 10-100-fold higher affinities than [3H]ketanserin for agonist-state sites. pmid:3350047

Drug affinities at [¹²⁵I]-R-(−)-DOI-labeled sites show high correlation with [⁷⁷Br]-R-(−)-DOB-labeled sites (r = 0.93, p < 0.01), confirming these radioligands label overlapping 5-HT₂A binding populations.supported

Correlation between drug affinities for 125I-DOI-labeled sites and 77Br-R(-)-DOB-labeled sites (r=0.93). Defined 5-HT2A binding site subtype. pmid:2795135

The desmethyl compound additionally binds 5-HT₁A, 5-HT₁B, and 5-HT₁C receptors with significant affinity, while DOB's alpha-methyl group confers selectivity for the 5-HT₂ subtypesupported

DOB is more selective than its desmethyl derivative for 5-HT2 receptors. pmid:3211969

A significant correlation exists between drug potencies at (R)-(−)-[⁷⁷Br]DOB-labeled sites and human hallucinogenic potencies across a series of phenylalkylamine and indolealkylamine compounds (r = 0.89, p < 0.01).supported

Significant correlation with human hallucinogenic potency (r=0.89). pmid:3173334

However, broad receptor profiling through the NIMH Psychoactive Drug Screening Program (PDSP) indicates phenylalkylamines interact with up to 42 of 49 tested receptor sites, suggesting DOB-class compounds are less selective than traditional binding studies imply.supported

Phenylalkylamines interact with 42 of 49 sites. Diversity of receptor interaction underlies qualitative diversity. journal.pone.0009019

R-(−)-DOB behaves as a partial agonist at 5-HT₂A with approximately 50% maximal efficacy in calcium mobilization. 5-HT₂A activation engages dual signaling cascades — Gq/G₁₁-mediated phospholipase C activation and β-arrestin2 recruitment — and structure-activity relationships for biased agonism across these pathways have been mapped for the phenylalkylamine class.supported

R(-)-DOB behaved as partial agonist (~50% efficacy) in 5-HT2-mediated calcium mobilization assay. pmid:15537358

R-(−)-DOB behaves as a partial agonist at 5-HT₂A with approximately 50% maximal efficacy in calcium mobilization. 5-HT₂A activation engages dual signaling cascades — Gq/G₁₁-mediated phospholipase C activation and β-arrestin2 recruitment — and structure-activity relationships for biased agonism across these pathways have been mapped for the phenylalkylamine class.supported

Biased agonism analysis of phenylalkylamine 5-HT2A agonists; DOB included; beta-arrestin2 vs miniGαq recruitment. acschemneuro.3c00267

The benzodifuran-constrained analog Bromo-DragonFLY achieves higher potency (ED₅₀ = 0.20 μmol/kg)supported

Bromo-DragonFLY (DOB-DFLY) had higher potency (ED50=0.20 μmol/kg). j.neuropharm.2018.10.037

In locus coeruleus electrophysiology, the potency rank order is (−)-DOB > DOM > (+)-DOB; the inactive positional isomer SL-7161 produced no effect on LC unit activity, supporting pharmacological specificity.supported

Rank order of potency in locus coeruleus: (-)-DOB > DOM > (+)-DOB. Inactive positional isomer SL-7161 did not affect LC activity. pmid:3816969

Its tritiated and brominated radioligand forms ([³H]DOB and [⁷⁷Br]DOB) have been instrumental in characterizing the 5-HT₂A receptor binding site and establishing the correlation between receptor affinity and human hallucinogenic potencysupported

(R)-(-)-[77Br]DOB labeled sites in rat cortical membranes with KD = 0.60 nM; significant correlation with human hallucinogenic potency (r=0.89). pmid:3173334

DOB acts as a partial agonist at 5-HT₂A receptors with subnanomolar affinity (Kᵢ = 0.2 nM for the active R-(−) enantiomer; ~50% efficacy in calcium mobilization assays). 5-HT₂A activation drives both Gq/G₁₁-mediated signaling and β-arrestin2 recruitment, and the 2,5-dimethoxy motif is critical for in vivo potency beyond its contribution to receptor binding alone.supported

R(-)-DOB Ki = 0.2 nM at 5-HT2A. R(-)-DOB behaved as partial agonist (~50% efficacy) in 5-HT2-mediated calcium mobilization assay. pmid:15537358

DOB acts as a partial agonist at 5-HT₂A receptors with subnanomolar affinity (Kᵢ = 0.2 nM for the active R-(−) enantiomer; ~50% efficacy in calcium mobilization assays). 5-HT₂A activation drives both Gq/G₁₁-mediated signaling and β-arrestin2 recruitment, and the 2,5-dimethoxy motif is critical for in vivo potency beyond its contribution to receptor binding alone.supported

Biased agonism analysis of phenylalkylamine 5-HT2A agonists; DOB included; beta-arrestin2 vs miniGαq recruitment. acschemneuro.3c00267

DOB acts as a partial agonist at 5-HT₂A receptors with subnanomolar affinity (Kᵢ = 0.2 nM for the active R-(−) enantiomer; ~50% efficacy in calcium mobilization assays). 5-HT₂A activation drives both Gq/G₁₁-mediated signaling and β-arrestin2 recruitment, and the 2,5-dimethoxy motif is critical for in vivo potency beyond its contribution to receptor binding alone.supported

2,5-dimethoxy motif removal modestly reduces binding but significantly reduces HTR in vivo. acschemneuro.0c00129

DOB produces predominantly LSD-like hallucinogenic effects with an amphetamine-like stimulant componentsupported

DOB predominantly LSD-like with some amphetamine-like activity in chronic spinal dog model. pmid:272982

The safety margin is extremely narrow: active doses (1–3 mg) lie in close proximity to toxic doses, and one confirmed fatality (serum DOB 19 ng/mL) has been documented at an unknown ingested dosesupported

One died 6 days later (serum 19 ng/mL) of convulsions and metabolic acidosis. pmid:15979834

Claim in summary — inconclusiveinconclusiveworking →

The alpha-methyl group distinguishes DOB from 2C-B and confers both increased 5-HT₂ selectivity and the metabolic resistance typical of amphetamines.supported

DOB is more selective than its desmethyl derivative for 5-HT2 receptors. pmid:3211969

The 2,5-dimethoxy substitution pattern is critical: removing either methoxy group from the DOB scaffold modestly reduces 5-HT₂A binding affinity in vitro but profoundly attenuates the head-twitch response in vivo, indicating the dimethoxy motif plays a mechanistic role beyond simple receptor binding.supported

2,5-dimethoxy motif removal modestly reduces binding but significantly reduces HTR in vivo. acschemneuro.0c00129

The R-(−) enantiomer is the pharmacologically active form (eutomer), with Kᵢ = 0.2 nM at 5-HT₂A — approximately 4-fold higher affinity than the racemate (Kᵢ = 0.79 nM)supported

R(-)-DOB Ki = 0.2 nM at 5-HT2A. pmid:15537358

The R-(−) enantiomer is the pharmacologically active form (eutomer), with Kᵢ = 0.2 nM at 5-HT₂A — approximately 4-fold higher affinity than the racemate (Kᵢ = 0.79 nM)supported

DOB itself Ki = 0.79 nM at [3H]DOB-labeled central 5-HT2 serotonin receptors. pmid:3211969

The S-(+) enantiomer is significantly less potent, as demonstrated in locus coeruleus electrophysiology where the potency rank order is (−)-DOB > dom > (+)-DOBsupported

Rank order of potency in locus coeruleus: (-)-DOB > DOM > (+)-DOB. pmid:3816969

Claim in chemistry — not_supportednot supportedworking →

This conformational constraint increases in vivo potency (ED₅₀ = 0.20 vs 0.75 μmol/kg in mouse HTR) but also dramatically increases toxicity risk, with documented fatalities from arterial vasospasm and limb ischemiasupported

DOB ED50 = 0.75 μmol/kg in mouse head-twitch response (HTR) assay. Bromo-DragonFLY (DOB-DFLY) had higher potency (ED50=0.20 μmol/kg). j.neuropharm.2018.10.037

This conformational constraint increases in vivo potency (ED₅₀ = 0.20 vs 0.75 μmol/kg in mouse HTR) but also dramatically increases toxicity risk, with documented fatalities from arterial vasospasm and limb ischemiasupported

Pharmacological, chemical, toxicological overview of Bromo-DragonFLY (DOB-DFLY analog). Associated with acute intoxications and fatalities. pmid:21592070

The parent compound dom (4-methyl) was the first DOx compound studied in controlled human trialssupported

First controlled human study of DOM (STP), a close DOx analog. science.158.3801.669

In locus coeruleus electrophysiology, (−)-DOB is more potent than DOM, which is in turn more potent than (+)-DOB.supported

Rank order of potency in locus coeruleus: (-)-DOB > DOM > (+)-DOB. pmid:3816969

Selectivity: DOB shows higher 5-HT₂ selectivity; 2C-B additionally binds 5-HT₁A, 5-HT₁B, and 5-HT₁C receptors with significant affinitysupported

DOB is more selective than its desmethyl derivative for 5-HT2 receptors. pmid:3211969

DOB-labeled and DOI-labeled radioligand sites show high correlation (r = 0.93, p < 0.01), confirming that [³H]DOB and [¹²⁵I]DOI label the same 5-HT₂A binding populationsupported

Correlation between drug affinities for 125I-DOI-labeled sites and 77Br-R(-)-DOB-labeled sites (r=0.93). Defined 5-HT2A binding site subtype. pmid:2795135

The parent class entered the scientific literature through the identification of dom (2,5-dimethoxy-4-methylamphetamine, "STP") by Snyder, Faillace, and Hollister in 1967, who demonstrated it was approximately 100 times more potent than mescaline as a hallucinogen in controlled human trials.supported

First controlled human study of DOM (STP), a close DOx analog. ~100x more potent than mescaline in humans. science.158.3801.669

Claim in history — inconclusiveinconclusiveworking →

Radiolabeled forms — [³H]DOB and (R)-(−)-[⁷⁷Br]DOB — became standard radioligands for characterizing serotonin 5-HT₂ receptor binding sites in brain tissuesupported

(R)-(-)-[77Br]DOB labeled sites in rat cortical membranes with KD = 0.60 nM. pmid:3173334

Radiolabeled forms — [³H]DOB and (R)-(−)-[⁷⁷Br]DOB — became standard radioligands for characterizing serotonin 5-HT₂ receptor binding sites in brain tissuesupported

[3H]DOB as a radioligand gave 10-100-fold higher affinities than [3H]ketanserin for agonist-state sites. pmid:3350047

Peroutka and colleagues demonstrated in 1988 that drug potencies at (R)-(−)-[⁷⁷Br]DOB-labeled sites correlated significantly with human hallucinogenic potencies (r = 0.89, p < 0.01), a finding that helped establish 5-HT₂A agonism as the primary mechanism of psychedelic actionsupported

Significant correlation with human hallucinogenic potency (r=0.89). pmid:3173334

This radioligand work continues to inform structure-activity studies in the DOx class.supported

Comprehensive historical and pharmacological review of the DOx class... Reviews synthesis history, SAR, 5-HT2 receptor agonism, behavioral pharmacology, development as research tools. acsptsci.4c00157

5-HT₂A receptors are densely expressed on layer V pyramidal neurons in the prefrontal cortex — the cellular trigger for psychedelic-state inductionsupported

Psychedelics are agonists or partial agonists at brain 5-HT2A receptors on apical dendrites of neocortical pyramidal cells layer V. pr.115.011478

DOB's partial agonist profile (~50% efficacy) may produce a quantitatively different pattern of network disruption compared to higher-efficacy agonists, though this hypothesis has not been testedsupported

R(-)-DOB behaved as partial agonist (~50% efficacy) in 5-HT2-mediated calcium mobilization assay. pmid:15537358

Claim in neuroscience — inconclusiveinconclusiveworking →

The sole quantitative human data derive from the Balíková 2005 overdose case report:supported

Two men ingested DOB; one survived (serum 13 ng/mL), one died 6 days later (serum 19 ng/mL). First DOB documentation in Czech Republic. pmid:15979834

All metabolic data for DOB are inferred from 2C-B (the alpha-desmethyl analog) studied in hepatocytes of six species including humansupported

2C-B (alpha-desMe analog of DOB) metabolized by hepatocytes from 6 species. Large inter-individual human differences. pmid:15590110

One confirmed overdose case report involving two patients who ingested an unknown quantity of DOB sold as an "LSD-like" designer drug. This case established serum concentration–outcome associations (13 ng/mL non-fatal; 19 ng/mL fatal) but provides no controlled pharmacological data.supported

Two men ingested DOB; one survived (serum 13 ng/mL), one died 6 days later (serum 19 ng/mL) of convulsions and metabolic acidosis. pmid:15979834