 Chemical structure of (±)-DOB | |
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| Other names | DOB; 4-Bromo-2,5-dimethoxyamphetamine; Brolamfetamine; Brolamphetamine; Bromo-DMA; 2,5-Dimethoxy-4-bromo-α-methylphenethylamine; 4-Bromo-2,5-dimethoxyphenyl-isopropylamine |
| Routes of administration | Oral |
| Drug class | Serotonin5-HT2 receptoragonist;Serotonergic psychedelic;Hallucinogen |
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| Formula | C11H16BrNO2 |
| Molar mass | 274.158 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 63–65 °C (145–149 °F) (207–208 °Chydrochloride) |
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2,5-Dimethoxy-4-bromoamphetamine (DOB), also known asbrolamfetamine (INNTooltip International Nonproprietary Name),[2] is apsychedelic drug of thephenethylamine,amphetamine, andDOx families.[3] For many years, prior to the discovery of newer agents such asDOTFM,FLY compounds likeBromo-DragonFLY, andNBOMe compounds like25I-NBOMe, DOB was the mostpotent known phenethylamine psychedelic.[3]
The drug acts as anagonist of theserotonin5-HT2 receptors, including of the serotonin5-HT2A receptor.[4][5]
DOB was firstsynthesized byAlexander Shulgin in 1967 and was described by him and his colleagues in thescientific literature in 1971.[6][7] Shulgin subsequently further described the effects of DOB in his 1991 bookPiHKAL (Phenethylamines I Have Known and Loved).[6]
In his bookPiHKAL,Alexander Shulgin gives the dose range of DOB as 1 to 3 mg and itsduration as 18 to 30 hours.[6] In other publications, he specifies the dose range as 2 to 3 mg forracemic DOB and 1 to 2 mg for the preferentially active (R)-DOBenantiomer, while the duration is stated as being extremely long, a plateau occurring between 4 to 10 hours, and returning to baseline after 24 to 36 hours.[3] DOB was described as producing effects such asclosed-eye andopen-eyepsychedelic visuals andintrospection, among others.[6][3]
At a low sub-hallucinogenic dose of 0.4 mg DOB, the drug was alsopsychoactive and produced effects including enhancedvisual perception, some strengthening of colors, enrichedemotional affect, a comfortable and good feeling, and colorful and importantdreams.[3]
Side effects of DOB includebody load,muscle tremors,muscle cramps,attention lapses described as "littlefugue states",sleeping difficulties, andbizarre dreams.[3]
Overdose of DOB has been reported to producecardiovascular symptoms andconvulsions.[3] Excessively high doses of DOB may cause diffusearterial spasm.[8] The vasospasm responded readily to intra-arterial and intravenousvasodilators, such astolazoline.[8] A 35 mg overdose resulted in death, while a 75 mg overdose in a person withtolerance resulted inergotism-like complications that requiredamputation.[3]
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 2,550–7,904 |
| 5-HT1B | 941 |
| 5-HT1D | 636 |
| 5-HT1E | 556–1,427 |
| 5-HT1F | ND |
| 5-HT2A | 0.6–81 (Ki) 0.52–50 (EC50Tooltip half-maximal effective concentration) 57–105% (EmaxTooltip maximal efficacy) |
| 5-HT2B | 2.9–44 (Ki) 2.82–65 (EC50) 70–100% (Emax) |
| 5-HT2C | 1.3–78 (Ki) 0.25–102 (EC50) 58–112% (Emax) |
| 5-HT3 | >10,000 |
| 5-HT4 | ND |
| 5-HT5A | 5,311 |
| 5-HT6 | 5,535 |
| 5-HT7 | 506 |
| α1A,α1B | >10,000 |
| α1D | ND |
| α2A | 4,266 |
| α2B | 1,527 |
| α2C | 594 |
| β1 | 2,425 |
| β2 | 303 |
| D1,D2 | >10,000 |
| D3 | 808 |
| D4,D5 | >10,000 |
| H1 | 9,120 |
| H2–H4 | >10,000 |
| M1,M2 | >10,000 |
| M3 | 1,152 |
| M4,M5 | >10,000 |
| TAAR1 | >1,000 |
| I1 | 1,596 |
| σ1 | 2,193 |
| σ2 | >10,000 |
| SERTTooltip Serotonin transporter | 8,538 (Ki) |
| NETTooltip Norepinephrine transporter | >10,000 (Ki) |
| DATTooltip Dopamine transporter | >10,000 (Ki) |
| MAO-ATooltip Monoamine oxidase A | 100,000 (IC50Tooltip half-maximal inhibitory concentration) (rat) |
| MAO-BTooltip Monoamine oxidase B | >100,000 (IC50) (rat) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified.Refs:[9][10][4][11][12][13][14][15][5][16][17] | |
DOB is aserotonin5-HT2A,5-HT2B, and5-HT2C receptoragonist.[4][5] Its psychedelic effects are mediated by itsagonistic properties at the 5-HT2A receptor. Due to its selectivity, DOB is often used in scientific research when studying the5-HT2 receptor subfamily.
It is a very weakagonist of the humantrace amine-associated receptor 1 (TAAR1) and a weak agonist of therhesus monkey TAAR1.[17][5] In contrast to theserotonin releasing agentMDMA, DOB does not produceprotein kinase C (PKC) activation in the brains of rodentsin vivo.[18][19] The PKC activation by MDMA appears to be dependent onuptake by theserotonin transporter (SERT).[18][19]
DOB has been found to reduceaggression in rats.[20][21]
DOB is one of the most potent compounds inPiHKAL; while the active dose is similar to that ofDOI, another psychedelic amphetamine, DOB has been shown to have a higher efficacy in triggering downstream effects mediated by serotonin 5-HT2 receptors.[22]
The full name of the chemical is 2,5-dimethoxy-4-bromoamphetamine. DOB has astereocenter andR-(−)-DOB is theeutomer. This is an important finding as it is suggestive that it is targeting different receptors relative to most otherphenethylamines (e.g.MDMA) where theR-isomer serves as thedistomer.
Omission of the amphetamine related α-methyl leads to2C-B, a compound that possesses a lower affinity for the 5-HT2A receptor and is a weaker receptor agonist.[citation needed] Otheranalogues of DOB include4C-B,Bromo-DragonFLY,DOB-FLY, and25B-NBOMe, among others.
DOB was firstsynthesized byAlexander Shulgin in 1967.[6] It was first described in thescientific literature in a paper by Shulgin,Claudio Naranjo, and another colleague in 1971.[7] TheINNTooltip International Nonproprietary Name of DOB,brolamfetamine, was proposed and recommended by theWorld Health Organization (WHO) in 1986.[23][24] This was the same year that theMultidisciplinary Association for Psychedelic Studies (MAPS) was founded.[25] DOB was registered with the WHO as a supposed "anorexic" (appetite suppressant).[26]
Internationally, DOB is a Schedule I substance under theConvention on Psychotropic Substances and the drug is legal only for medical, industrial or scientific purposes.[27]
Listed as aSchedule 1 as it is an analogue of amphetamine.[28]
DOB is considered a Schedule 9 prohibited substance in Australia under thePoisons Standard (February 2017).[29] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[29]
Schedule I, possession of at least 10 mg is a criminal offence.[30]
DOB is aClass A drug in the United Kingdom under theMisuse of Drugs Act 1971.
DOB is aSchedule Icontrolled substance under federal law in theUnited States.[31] It was scheduled in 1973.[32]
MDMA manifests its acute psychotropic and neurotoxic effects by releasing 5-HT from nerve endings. MDMA also shows a moderate agonist-like affinity (1.5-3.2 mM [(sic)]) for the central 5-HT2 receptor. Activation of this receptor stimulates the translocation/activation of protein kinase C (PKC) and the release of Ca2+ from intracellular sequestration sites. MDMA has already been shown to increase [Ca2+], and this may proceed through the activation of this receptor. [...] In vivo, both MDMA and PCA were found to produce a lasting translocation of [protein kinase C (PKC)] in the cortex and hippocampus of treated rats. Fluoxetine, a 5-HT uptake inhibitor, prevents PKC translocation, while ketanserin, a 5-HT2A antagonist, acts similarly but a diminished efficacy. Non-neurotoxic drugs like fluoxetine, DOB, and cocaine were devoid of MDMA's long-term PKC translocating abilities, and suggests that receptor stimulation alone is not the sole mechanism. In synaptosomes, MDMA was effective at producing PKC translocation by binding to the 5-HT uptake carner. This in vitro response [of] fluoxetine reverses this response and demonstrates that MDMA translocates PKC within the 5-HT nerve terminal.
Another 5HT2A receptor partial agonist, DOB, has a marginally higher affinity for the 5HT2A receptor (in its low affinity state) than DOI (Roth et al. 1997), and in the water competition (WC) test it has been shown to block defensive aggression in rats. Interestingly, DOI also reduced the number of offensive aggressive behaviors (i.e., attacks, greater latency to first attack, shorter attack duration) in the same animals that exhibited DOI-induced reductions in defensive behaviors during the WC test (Muehlenkamp et al. 1995).
