Chemistry:Scaline

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A scaline, also known as a substituted mescaline analogue and typically but not always a 4-substituted 3,5-dimethoxyphenethylamine, is an analogue of the phenethylamine serotonergic psychedelic mescaline (3,4,5-trimethoxyphenethylamine).[1][2][3][4][5][6][7]

Other related compounds include the 2C (4-substituted 2,5-dimethoxyphenethylamine) and DOx (4-substituted 2,5-dimethoxyamphetamine) compounds as well as 3,4,5-trimethoxyamphetamine (TMA) and other 4-substituted 3,5-dimethoxyamphetamines (3C drugs).[1][2][3][4] They are also mescaline analogues, but the 2C and DOx drugs have a methoxy group at the 2 position instead of the 3 position of the phenyl ring, while TMA is an amphetamine rather than a phenethylamine.[1][2][3][4]

The pharmacology of mescaline analogues has been studied.[8][9][10] Mescaline analogues, or 4-substituted 3,5-dimethoxyphenethylamines specifically, tend to be much less potent than the 2C and DOx drugs.[1][3][2] This relates to the fact that the 2,4,5-substitution pattern tends to be optimal in terms of receptor affinity and potency.[1][11] However, mescaline analogues are frequently much more potent than mescaline.[1][3]

Substituted mescaline analogues have been extensively characterized by Alexander Shulgin and described in his books such as PiHKAL (Phenethylamines I Have Known and Loved)[6] and The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds[7] as well as in his literature reviews.[1][3][4][5] They have also been studied by David E. Nichols[12][13][14] and Daniel Trachsel,[15][8][10] among other researchers.

Use and effects

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Interactions

Pharmacology

Pharmacodynamics

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Society and culture

Canada

Mescaline and 3,4,5-trimethoxyamphetamine (TMA) are the only scalines (and derivatives) that are controlled substances in Canada as of 2025.[21]

List of scalines

4-Substituted

  • Allylescaline (AL) (4-allyloxy-3,5-dimethoxyphenethylamine)
  • Amylescaline (4-n-amyloxy-3,5-dimethoxyphenethylamine)
  • Benzscaline (BZ) (4-benzyloxy-3,5-dimethoxyphenethylamine)
  • Biscaline (4-phenyl-3,5-dimethoxyphenethylamine)
  • Buscaline (B) (4-butoxy-3,5-dimethoxyphenethylamine)
  • Cyclopropylmescaline (CPM) (4-cyclopropylmethoxy-3,5-dimethoxyphenethylamine)
  • Cycloproscaline (CP) (4-cyclopropoxy-3,5-dimethoxyphenethylamine)
  • 4-Desmethylmescaline (DESMETHYL) (4-hydroxy-3,5-dimethoxyphenethylamine)
  • 4-Desoxymescaline (4-methyl-3,5-dimethoxyphenethylamine)
  • Difluoroescaline (DFE) (multiple forms)
  • Difluoroisoproscaline (DFIP) (multiple forms)
  • Difluoromescaline (DFM) (4-difluoromethoxy-3,5-dimethoxyphenethylamine)
  • Escaline (E) (4-ethoxy-3,5-dimethoxyphenethylamine)
  • Fluoroescaline (FE) (multiple forms)
  • Fluoromescaline (FM) (4-fluoromethoxy-3,5-dimethoxyphenethylamine)
  • Fluoroproscaline (FP) (multiple forms)
  • Hexylescaline (4-n-hexyloxy-3,5-dimethoxyphenethylamine)
  • Isobuscaline (IB) (4-isobutoxy-3,5-dimethoxyphenethylamine)
  • Isoproscaline (IP) (4-isopropoxy-3,5-dimethoxyphenethylamine)
  • Methallylescaline (MAL) (4-methylallyloxy-3,5-dimethoxyphenethylamine)
  • Phenescaline (4-phenylethoxy-3,5-dimethoxyphenethylamine)
  • Propynylscaline (4-propynyloxy-3,5-dimethoxyphenethylamine)
  • Proscaline (P) (4-propoxy-3,5-dimethoxyphenethylamine)
  • Septylescaline (4-n-heptyloxy-3,5-dimethoxyphenethylamine)
  • 4-Thiobuscaline (4-TB) (4-butylthio-3,5-dimethoxyphenethylamine)
  • 4-Thioescaline (4-TE) (4-ethylthio-3,5-dimethoxyphenethylamine)
  • 4-Thiomescaline (4-TM) (4-methylthio-3,5-dimethoxyphenethylamine)
  • 4-Thioproscaline (4-TP) (4-propylthio-3,5-dimethoxyphenethylamine)

3- or 5-Extended

  • Asymbescaline (ASB) (3,4-diethoxy-5-methoxyphenethylamine)
  • Metadifluoromescaline (MDFM) (3,4-dimethoxy-5-difluoromethoxyphenethylamine)
  • Metaescaline (ME) (3-ethoxy-4,5-dimethoxyphenethylamine)
  • Metaproscaline (MP) (3,4-dimethoxy-5-propoxyphenethylamine)
  • Symbescaline (SB) (4-methoxy-3,5-diethoxyphenethylamine)
  • 4-Thioasymbescaline (4-TASB) (4-ethylthio-3-ethoxy-5-methoxyphenethylamine)
  • 4-Thiometaescaline (4-TME) (4-methylthio-3-ethoxy-5-methoxyphenethylamine)
  • 4-Thiosymbescaline (4-TSB) (4-methylthio-3,5-diethoxyphenethylamine)
  • 4-Thiotrescaline (4-T-TRIS; 4-thiotrisescaline) (4-ethylthio-3,5-diethoxyphenethylamine)
  • Trescaline (TRIS; trisescaline) (3,4,5-triethoxyphenethylamine)

3- or 5-Replaced

  • 3-Desmethylmescaline (3-DESMETHYL) (3,4-dimethoxy-5-hydroxyphenethylamine)
  • 3-Thioasymbescaline (3-TASB) (3-ethylthio-4-ethoxy-5-methoxyphenethylamine)
  • 5-Thioasymbescaline (5-TASB) (3,4-diethoxy-5-methylthiophenethylamine)
  • 3-Thioescaline (3-TE) (3-methoxy-4-ethoxy-5-methylthiophenethylamine)
  • 3-Thiomescaline (3-TM) (3,4-dimethoxy-5-methylthiophenethylamine)
  • 3-Thiometaescaline (3-TME) (3-ethylthio-4,5-dimethoxyphenethylamine)
  • 5-Thiometaescaline (5-TME) (3-ethoxy-4-methoxy-5-methylthiophenethylamine)
  • 3-Thiosymbescaline (3-TSB) (3-ethoxy-4-methoxy-5-ethylthiophenethylamine)
  • 3-Thiotrescaline (3-T-TRIS; 3-thiotrisescaline) (3,4-diethoxy-5-ethylthiophenethylamine)
  • 3,4,5-Trideoxymescaline (TMePEA) (3,4,5-trimethylphenethylamine)

2- or 6-Substituted

  • 2-Bromo-6-chloromescaline (2-bromo-6-chloro-3,4,5-trimethoxyphenethylamine)
  • 2-Bromo-6-methylmescaline (2-bromo-6-methyl-3,4,5-trimethoxyphenethylamine)
  • 2-Bromomescaline (2-bromo-3,4,5-trimethoxyphenethylamine)
  • 2-Chloromescaline (2-chloro-3,4,5-trimethoxyphenethylamine)
  • 2-Iodomescaline (2-iodo-3,4,5-trimethoxyphenethylamine)
  • 2-Methylmescaline (2-methyl-3,4,5-trimethoxyphenethylamine)
  • 2,6-Dibromomescaline (2,6-dibromo-3,4,5-trimethoxyphenethylamine)
  • 2,6-Dichloromescaline (2,6-dichloro-3,4,5-trimethoxyphenethylamine)
  • 2,6-Dimethylmescaline (2,6-dimethyl-3,4,5-trimethoxyphenethylamine)
  • 2,3,4,5,6-Pentamethoxyphenethylamine (PeMPEA; 2,6-dimethoxymescaline)
  • 2,3,4,5-Tetramethoxyphenethylamine (TeMPEA; TeMPEA-1; 2-methoxymescaline)

N-Substituted

α- or β-Substituted

  • BOM (β,3,4,5-tetramethoxyphenethylamine; β-methoxymescaline)
  • α-Ethylmescaline (AEM) (α-ethyl-3,4,5-trimethoxyphenethylamine)
  • β-HOM (3,4,5-trimethoxy-β-hydroxyphenethylamine; β-hydroxymescaline)
  • 3,4,5-Trimethoxyamphetamine (3,4,5-TMA; TMA; TMA-1; α-methylmescaline)

Cyclized

  • Bromojimscaline (1-(7-bromo-4,5,6-trimethoxy-2,3-dihydro-1H-inden-1-yl)methanamine)
  • Bromotomscaline (1-(5-bromo-2,3,4-trimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methanamine)
  • DEMPDHPCA-M (DEMPDHPCA-mescaline; N,N-diethyl-1-methyl-5-(3,4,5-trimethoxyphenyl)-1,2,3,6-tetrahydropyridine-3-carboxamide)
  • Flyscaline (mescaline-FLY)
  • Jimscaline (1-(4,5,6-trimethoxy-2,3-dihydro-1H-inden-1-yl)methylamine)
  • Tomscaline (1-(2,3,4-trimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine)

Other compounds

  • 4-D (4-trideuteromescaline; 4-trideuteromethoxy-3,5-methoxyphenethylamine)
  • 3,5-Dimethoxyphenethylamine (3,5-DMPEA; 4-desmethoxymescaline)
  • Beta-D (β-D; β-dideuteromescaline) (3,4,5-trimethoxy-β-dideuterophenethylamine; β-dideuteromescaline)
  • Isomescaline (IM) (2,3,4-trimethoxyphenethylamine)
  • Lophophine (2C-MMDA; 5-methoxy-MDPEA; MMDPEA; 3-methoxy-4,5-methylenedioxyphenethylamine)
  • 2-Thioisomescaline (2-TIM) (2-methylthio-3,4-dimethoxyphenethylamine)
  • 3-Thioisomescaline (3-TIM) (3-methylthio-2,4-dimethoxyphenethylamine)
  • 4-Thioisomescaline (4-TIM) (4-methylthio-2,4-dimethoxyphenethylamine)

See also

  • Substituted methoxyphenethylamine
  • 3C (psychedelics) (4-substituted 3,5-dimethoxyamphetamines)
  • PiHKAL (Phenethylamines I Have Known and Loved)
  • The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "Basic Pharmacology and Effects". Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. 2003. pp. 67–137. ISBN 978-0-12-433951-4. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6. Retrieved 1 February 2025. 
  2. 2.0 2.1 2.2 2.3 "Mescaline analogs: substitutions at the 4-position". NIDA Res Monogr (22): 27–37. 1978. PMID 101882. https://archives.nida.nih.gov/sites/default/files/monograph22.pdf#page=38. 
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Structure-activity relationships of the classic hallucinogens and their analogs". NIDA Res Monogr 146: 74–91. 1994. PMID 8742795. https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79. 
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  5. 5.0 5.1 "Mescaline: the chemistry and pharmacology of its analogs". Lloydia 36 (1): 46–58. March 1973. PMID 4576313. https://bitnest.netfirms.com/external/Lloydia/36.1.46. 
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  8. 8.0 8.1 8.2 "Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines". Front Pharmacol 12. 2021. doi:10.3389/fphar.2021.794254. PMID 35222010. 
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  11. "1-[4-(3-Phenylalkyl)phenyl-2-aminopropanes as 5-HT(2A) partial agonists"]. Journal of Medicinal Chemistry 43 (16): 3074–3084. August 2000. doi:10.1021/jm9906062. PMID 10956215. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=ad45346022bb7e6e1bec1fbfbcca3bcb60b13058. 
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  15. 15.0 15.1 Trachsel, D.; Lehmann, D.; Enzensperger, C. (2013) (in de). Phenethylamine: von der Struktur zur Funktion. Nachtschatten-Science (1 ed.). Solothurn: Nachtschatten-Verlag. ISBN 978-3-03788-700-4. OCLC 858805226. https://books.google.com/books?id=-Us1kgEACAAJ. Retrieved 31 January 2025. 
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