Chemistry:Desoxybromoscaline

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Desoxybromoscaline (DBR), also known as 4-bromo-3,5-dimethoxyphenethylamine (4-Br-3,5-DMPEA) or as 4-bromomescaline, is a serotonin receptor modulator of the phenethylamine and desoxyscaline families related to the psychedelic drug mescaline.[1][2][3] It is the analogue of mescaline in which the methoxy group at the 4 position has been replaced with a bromine atom.[1][2][3] The drug is also the phenethylamine (α-desmethyl) analogue of 4-Br-3,5-DMA and a positional isomer of 2C-B (4-Br-2,5-DMPEA).[1][2][3]

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin briefly mentions desoxybromoscaline and states that it has never been tested in humans.[1] As such, its properties and effects in humans are unknown.[1]

Pharmacology

Pharmacodynamics

Desoxybromoscaline has been found to be a potent serotonin receptor agonist in the sheep umbilical artery (EC50 = 185 nM).[1][2][4] It was 7.6-fold more potent than mescaline in this assay.[4] In a subsequent study, the drug showed high affinity for the serotonin 5-HT2A receptor (K0.5 = 45 nM).[5] Its affinity for this receptor was approximately 18-fold higher than that of mescaline.[5] Later on, the activities of desoxybromoscaline have been further described, with it showing affinity for all three serotonin 5-HT2 receptors and acting as a full agonist of the serotonin 5-HT2A receptor and as a partial agonist of the serotonin 5-HT2B receptor.[3]

Chemistry

Synthesis

The chemical synthesis of desoxybromoscaline has been described.[3]

Analogues

Analogues of desoxybromoscaline include mescaline, desoxy (desoxymescaline; 4-desoxymescaline; 4-methylmescaline; 4-Me-3,5-DMPEA), 4-O-desmethylmescaline (desmethyl; 4-hydroxymescaline; 4-OH-3,5-DMPEA), 2C-B (4-Br-2,5-DMPEA), and 4-Br-3,5-DMA, among others.[1][2][5][3] 4-Br-3,5-DMA has been found to be a potent psychoactive drug in humans, though it did not produce clear hallucinogenic effects at tested doses of 3 to 10 mg orally and instead produced pronounced analgesic and tactile anesthetic effects among others.[1][6][7] On the other hand, desoxy (4-methylmescaline), a positional isomer of 2C-D, is a psychedelic drug similarly to mescaline at doses of 40 to 120 mg orally, albeit with distinct effects.[1][2] Daniel Trachsel has expressed great interest in desoxyscalines like desoxymescaline and desoxybromoscaline and has named and studied many of these compounds.[2][3]

History

Desoxybromoscaline was first described in the scientific literature by David E. Nichols and Alexander Shulgin and colleagues in 1977.[2][4][6] Subsequently, it was described by Shulgin in his book PiHKAL (Phenethylamines I Have Known and Loved) in 1991.[1]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. http://www.erowid.org/library/books_online/pihkal/pihkal.shtml.  "A mescaline analogue with a bromo atom in place of the 4-methoxyl group is an analogue of mescaline in exactly the same way that DOB (a very potent amphetamine) is an analog of TMA-2 (the original trisubstituted amphetamine). This analogue, 3,5-dimethoxy-4-bromoamphetamine 4-bromo-3,5-dimethoxyphenethylamine, has been found to be a most effective serotonin agonist, and it is a possibility that it could be a most potent phenethylamine. But, as of the present time, it has never been assayed in man."
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 (in de) Phenethylamine: von der Struktur zur Funktion. Nachtschatten-Science (1 ed.). Solothurn: Nachtschatten-Verlag. 2013. pp. 740–744. ISBN 978-3-03788-700-4. OCLC 858805226. https://books.google.com/books?id=-Us1kgEACAAJ. "[Translated:] Compounds 154-155 contain a halogen atom instead of the 4-alkyloxy group found in many known mescaline analogues. 4-BR (154) was tested by Nichols and Dyer for the correlation between lipophilicity and 5-HT agonist activity [103]. The 3C analogue 4-BR-3,5-DMA (155) was described by Shulgin for its activity in humans [19]; at a dose of 4-10 mg, no significant effects were observed (a certain, undefined effect was present for 8-12 h), but there were indications of analgesic effects. However, these could not be confirmed in an animal study [19]. [...] Shulgin investigated the effects of desoxymescaline (DESOXY; 164) in humans [19]. He mentions a dosage of 40-120 mg and a duration of action of 6-8 hours. The psychedelic color display of mescaline (1) does not appear to be present; however, the imagery induced by music with closed eyes was clearly evident. The initial results from DESOXY (164) suggest that further interesting substances of this type are possible. What would other homo-scalines without the oxygen in the 4-position show in vitro and in vivo? The substance desoxyescalin (DE; 166) is, at least sterically speaking, closer to mescaline (1) than DESOXY (164). Many other potentially interesting deoxy compounds are conceivable, such as 167-174, and it would be quite exciting to have the in vitro and in vivo data at hand to learn more about the properties of the 3,4,5-trisubstituted phenylalkylamines. Here, too, 3C analogs would be conceivable, a currently completely unexplored class. What would happen if one of the two MeO groups in DESOXY (164) or in 166-174 were replaced by an EtO, MeS, or EtS substituent? This results in countless theoretical combinations!" 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 ; Matthias Emanuel Liechti & Felix Lustenberger"Desoxyscaline derivatives with modified mescaline-like action" US patent 20230285327, published 14 September 2023, assigned to Mind Medicine, Inc. Data table
  4. ↑ 4.0 4.1 4.2 "Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogues". Journal of Medicinal Chemistry 20 (2): 299–301. February 1977. doi:10.1021/jm00212a022. PMID 836502. 
  5. ↑ 5.0 5.1 5.2 McCorvy JD (16 January 2013). Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics (Ph.D. thesis). Purdue University. Archived from the original on 15 May 2025. Retrieved 27 May 2025 – via Purdue e-Pubs.
  6. ↑ 6.0 6.1 "Directional lipophilic character in a series of psychotomimetic phenethylamine derivatives". Life Sciences 21 (4): 569–575. August 1977. doi:10.1016/0024-3205(77)90099-6. PMID 904435. 
  7. ↑ "Psychotomimetic Drugs: Structure-Activity Relationships". Stimulants. Boston, MA: Springer US. 1978. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6. https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6. "3.5.7. 4-Bromo-3,5-dimethoxyphenylisopropylamine: 4-Bromo-3,5-dimethoxyphenylisopropylamine (85) has been prepared (Barfknecht and Nichols, 1971) and found to be centrally active in man (Nichols et al., 1977). Threshold effects are first noted in the dose range 3-6 mg, and at 10 mg orally there are indications of both mental (psychotomimetic?) and physical (central analgesia) effects. The action of the drug appears to be complex, and a single assignment of its character will have to await additional studies." 



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