4-Bromo-3,5-dimethoxyamphetamine

4-Br-3,5-DMA
Clinical data
Other names	4-Bromo-3,5-dimethoxyamphetamine; 3,5-Dimethoxy-4-bromoamphetamine; 4,3,5-DOB; 4-Bromo-TMA; 4-Bromo-3,4,5-TMA
Routes of; administration	Oral
Drug class	Serotonin receptor modulator; Psychoactive drug; Analgesic; Tactile anesthetic
ATC code	None;
Pharmacokinetic data
Duration of action	8–12 hours
Identifiers
	IUPAC name 1-(4-bromo-3,5-dimethoxyphenyl)propan-2-amine;
CAS Number	32156-34-6 ;
PubChem CID	208044;
ChemSpider	180279 ;
UNII	5BN3H3UZ8R;
ChEMBL	ChEMBL104362 ;
CompTox Dashboard (EPA)	DTXSID30276857 ;
Chemical and physical data
Formula	C11H16BrNO2
Molar mass	274.158 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=C(C(=C(C=C1CC(C)N)OC)Br)OC;
	InChI InChI=1S/C11H16BrNO2/c1-7(13)4-8-5-9(14-2)11(12)10(6-8)15-3/h5-7H,4,13H2,1-3H3 ; Key:FAVLJTSHWBEOMA-UHFFFAOYSA-N ;
	(verify)

4-Br-3,5-DMA, also known as 4-bromo-3,5-dimethoxyamphetamine or as 4-bromo-TMA, is a psychoactive drug of the phenethylamine, amphetamine, and 3C families related to mescaline.^[1]^[2] It is the analogue of TMA in which the methoxy group at the 4 position has been replaced with a bromine atom.^[1]^[2] In addition, 4-Br-3,5-DMA is a positional isomer of DOB with the methoxy group at the 2 position located instead at the 3 position.^[1]^[2]

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved) and other publications, Alexander Shulgin lists 4-Br-3,5-DMA's dose range as 4 to 10 mg orally and its duration as 8 to 12 hours.^[1]^[2]^[3]^[4] In earlier publications, the dose range was listed as 3 to 6 mg orally and was described as producing threshold effects.^[3]^[4] The effects of 4-Br-3,5-DMA have been reported to include very shallow threshold effects to a "plus-two" on the Shulgin Rating Scale depending on dose, very little if any sensory distortion, pronounced analgesia or tactile anesthesia and numbing of the skin and extremities, and teeth rubbiness.^[1]^[3] Although it produces both mental and physical effects, there were no clear hallucinogenic or visual effects at tested doses.^[1]^[3] Shulgin said that it is a "remarkably effective anesthetic to skin surfaces" taken systemically at his listed doses and suggested that it might be a "narcotic" rather than a psychedelic.^[1]

Pharmacology

Pharmacodynamics

4-Br-3,5-DMA shows affinity for the serotonin 5-HT_2A and 5-HT_2C receptors (K_i = 210 nM and 570 nM, respectively).^[5] Its affinities for these receptors were approximately 7-fold and 9-fold lower than those of DOB, respectively.^[5] Although 4-Br-3,5-DMA produced analgesic effects in humans, this could not subsequently be confirmed in thorough animal studies, at least in rodents.^[1]

Chemistry

Synthesis

The chemical synthesis of 4-Br-3,5-DMA has been described.^[1]^[5]^[6]

Analogues

Analogues of 4-Br-3,5-DMA include mescaline and other scalines, TMA and other 3C-scalines, DOB (4-Br-2,5-DMA), meta-DOB (5-Br-2,4-DMA), and 3-DOB (3-Br-2,5-DMA; iso-DOB), among others.^[1]^[2]

History

4-Br-3,5-DMA was first described in the scientific literature by David E. Nichols and colleagues in 1971.^[3]^[7] Subsequently, it was described in greater detail by Shulgin in PiHKAL in 1991.^[1]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. http://erowid.org/library/books_online/pihkal/pihkal018.shtml}}
^ ^a ^b ^c ^d ^e ^f Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4. Archived from the original on 13 July 2025. Two positional isomers [...] of these halogenated amphetamine derivatives [(e.g. DOB)] have been clinically explored, and all are less active than their parent prototypes. The interchanging of the 5-methoxy group and the bromine atom of DOB produces META-DOB (5-bromo-2,4-dimethoxyamphetamine) which proved to develop a complex toxic syndrome in the 50 to 100mg range. The relocation of the 2-methoxy group to the 3-position produces 4-Br-3,5-DMA (4-bromo-3,5-dimethoxyamphetamine) which is a remarkably effective anesthetic to skin surfaces at 4 to 10 mg orally. [...]
^ ^a ^b ^c ^d ^e Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6. 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.
^ ^a ^b Nichols DE, Shulgin AT, Dyer DC (August 1977). "Directional lipophilic character in a series of psychotomimetic phenethylamine derivatives". Life Sci. 21 (4): 569–575. doi:10.1016/0024-3205(77)90099-6. PMID 904435. Archived from the original on 2025-07-12. This model has new been used successfully for predictive purposes. For example, 3,5-dimethoxy-4-bromophenylisopropylamine, compound 27, was predicted to have high potency based on its log P value and in vitro activity in thin preparation far its 2 carbon homolog 5. Subsequent testing revealed that this compound elicits central effects in man at a dose in the range 3-6 mg.
^ ^a ^b ^c Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, Glennon RA (August 2000). "1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists". J Med Chem. 43 (16): 3074–3084. doi:10.1021/jm9906062. PMID 10956215.
^ Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC 1194694085.
^ Antun F, Smythies JR, Benington F, Morin RD, Barfknecht CF, Nichols DE (January 1971). "Native fluorescence and hallucinogenic potency of some amphetamines". Experientia. 27 (1): 62–63. doi:10.1007/BF02137743. PMID 5549244.

External links

[PiHKAL-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. http://erowid.org/library/books_online/pihkal/pihkal018.shtml}}

[Shulgin2003-2] ^ ^a ^b ^c ^d ^e ^f Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4. Archived from the original on 13 July 2025. Two positional isomers [...] of these halogenated amphetamine derivatives [(e.g. DOB)] have been clinically explored, and all are less active than their parent prototypes. The interchanging of the 5-methoxy group and the bromine atom of DOB produces META-DOB (5-bromo-2,4-dimethoxyamphetamine) which proved to develop a complex toxic syndrome in the 50 to 100mg range. The relocation of the 2-methoxy group to the 3-position produces 4-Br-3,5-DMA (4-bromo-3,5-dimethoxyamphetamine) which is a remarkably effective anesthetic to skin surfaces at 4 to 10 mg orally. [...]

[IversenIversenSnyder1978-3] Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6. 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.

[NicholsShulginDyer1977-4] Nichols DE, Shulgin AT, Dyer DC (August 1977). "Directional lipophilic character in a series of psychotomimetic phenethylamine derivatives". Life Sci. 21 (4): 569–575. doi:10.1016/0024-3205(77)90099-6. PMID 904435. Archived from the original on 2025-07-12. This model has new been used successfully for predictive purposes. For example, 3,5-dimethoxy-4-bromophenylisopropylamine, compound 27, was predicted to have high potency based on its log P value and in vitro activity in thin preparation far its 2 carbon homolog 5. Subsequent testing revealed that this compound elicits central effects in man at a dose in the range 3-6 mg.

[DowdHerrick-DavisEgan2000-5] Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, Glennon RA (August 2000). "1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists". J Med Chem. 43 (16): 3074–3084. doi:10.1021/jm9906062. PMID 10956215.

[Nichols1973-6] Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC 1194694085.

[AntunSmythiesBenington1971-7] Antun F, Smythies JR, Benington F, Morin RD, Barfknecht CF, Nichols DE (January 1971). "Native fluorescence and hallucinogenic potency of some amphetamines". Experientia. 27 (1): 62–63. doi:10.1007/BF02137743. PMID 5549244.

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