2C (psychedelics)

General structure of a 2C compound

2C (2C-x) is a general name for the family of psychedelic phenethylamines containing methoxy groups on the 2 and 5 positions of a benzene ring.[1][2][3] Most of these compounds also carry lipophilic substituents at the 4 position, usually resulting in more potent and more metabolically stable and longer acting compounds.[4]

Most of the currently known 2C compounds were first synthesized by Alexander Shulgin in the 1970s and 1980s and published in his book PiHKAL (Phenethylamines i Have Known And Loved).[3] Shulgin also coined the term 2C, being an acronym for the 2 carbon atoms between the benzene ring and the amino group.[5][1][3]

Pharmacology

Pharmacodynamics

The 2C drugs act as agonists of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors.[6][7][8][9] Most of the 2C drugs have much lower affinity for the serotonin 5-HT1A receptor than for the serotonin 5-HT2A receptor.[6][7][8] Their psychedelic effects are thought to be mediated specifically by activation of the serotonin 5-HT2A receptor.[7][9]

Unlike many other phenethylamines, 2C drugs, including 2C-C, 2C-D, 2C-E, 2C-I, and 2C-T-2 among others, are inactive as monoamine releasing agents and reuptake inhibitors.[10][7][6][9]

Many of the 2C drugs are agonists of the rat, mouse, and/or human trace amine-associated receptor 1 (TAAR1).[11][12][6]

Pharmacokinetics

The 2C drugs are orally active and most have doses in the range of 10 to 60 mg and durations in the range of 4 to 12 hours.[1] They are metabolized by O-demethylation and deamination (by monoamine oxidases).[1]

List of 2C drugs[1]

Nomenclature R3 R4 2D Structure CAS number
2C-B H Br 66142-81-2
2C-Bn H CH2C6H5
2C-Bu H CH2CH2CH2CH3
2C-C H Cl 88441-14-9
2C-C-3 [13] Cl Cl
2C-CN H C≡N 88441-07-0
2C-D H CH3 24333-19-5
2C-E H CH2CH3 71539-34-9
2C-EF H CH2CH2F 1222814-77-8
2C-F H F 207740-15-6
2C-G CH3 CH3 207740-18-9
2C-G-1 CH2
2C-G-2 (CH2)2
2C-G-3 (CH2)3 207740-19-0
2C-G-4 (CH2)4 952006-59-6
2C-G-5 (CH2)5 207740-20-3
2C-G-6 (CH2)6
2C-G-N (CH)4 207740-21-4
2C-H H H 3600-86-0
2C-I H I 69587-11-7
2C-iP H CH(CH3)2 1498978-47-4
2C-TBU H C(CH3)3
2C-CP H C3H5 2888537-46-8
2C-CPE H C5H9
2C-N H NO2 261789-00-8
2C-NH2 H NH2 168699-66-9
2C-PYR H Pyrrolidine
2C-PIP H Piperidine
2C-O H OCH3 15394-83-9
2C-O-4 H OCH(CH3)2 952006-65-4
2C-MOM [14] H CH2OCH3
2C-P H CH2CH2CH3 207740-22-5
2C-Ph H C6H5
2C-Se H Se CH3 1189246-68-1
2C-T H SCH3 61638-09-3
2C-T-2 H SCH2CH3 207740-24-7
2C-T-3[15] H SCH2C(=CH2)CH3 648957-40-8
2C-T-4 H SCH(CH3)2 207740-25-8
2C-T-5[15]
2C-T-6[15]
2C-T-7 H S(CH2)2CH3 207740-26-9
2C-T-8 H SCH2CH(CH2)2 207740-27-0
2C-T-9[15] 207740-28-1
2C-T-10[15]
2C-T-11[15]
2C-T-12[15]
2C-T-13 H S(CH2)2OCH3 207740-30-5
2C-T-14[15]
2C-T-15 H SCH(CH2)2
2C-T-16[16] H SCH2CH=CH2 648957-42-0
2C-T-17 H SCH(CH3)CH2CH3 207740-32-7
2C-T-18[15]
2C-T-19 H SCH2CH2CH2CH3
2C-T-21 H S(CH2)2F 207740-33-8
2C-T-21.5[15] 648957-46-4
2C-T-22[15] 648957-48-6
2C-T-23[15]
2C-T-24[15]
2C-T-25[15]
2C-T-27[15] 648957-52-2
2C-T-28[15] 648957-54-4
2C-T-30[15]
2C-T-31[15]
2C-T-32[15]
2C-T-33[15]
2C-T-DFM H SCF2H
CYB210010[17] H SCF3
2C-T-DFP H SCH2CH2CF2H
2C-T-PARGY H SCH2C≡CH
2C-DFM [18]: 770  H CHF2
2C-TFM H CF3 159277-08-4
2C-TFE H CH2CF3
2C-PFE H CF2CF3
2C-PFS H SF5
2C-YN H C≡CH 752982-24-4
2C-V H CH=CH2
2C-AL[19] H CH2CH=CH2

Legality

Canada

As of October 12, 2016, the 2C-x family of substituted phenethylamines is a controlled substance (Schedule III) in Canada.[20]

See also

References

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  2. ^ Alexander Shulgin, Tania Manning and Paul F Daley. The Shulgin Index. Volume 1. Psychedelic Phenethylamines and Related Compounds. Transform Press, 2011. ISBN 978-0-9630096-3-0
  3. ^ a b c Barceloux, Donald G. (9 March 2012). Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Wiley. doi:10.1002/9781118105955.ch10. ISBN 978-0-471-72760-6.
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  5. ^ Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628.
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  13. ^ Takahashi M, Nagashima M, Suzuki J, Seto T, Yasuda I, Yoshida T. Creation and application of psychoactive designer drugs data library using liquid chromatography with photodiode array spectrophotometry detector and gas chromatography–mass spectrometry. Talanta, 15 Feb 2009, 77(4): 1245–1272. doi:10.1016/j.talanta.2008.07.062
  14. ^ Leth-Petersen S, Petersen IN, Jensen AA, Bundgaard C, Bæk M, Kehler J, Kristensen JL. 5-HT2A/5-HT2C receptor pharmacology and intrinsic clearance of N-benzylphenethylamines modified at the primary site of metabolism. ACS Chem. Neurosci., 16 Nov 2016, 7 (11), 1614–1619. doi:10.1021/acschemneuro.6b00265
  15. ^ a b c d e f g h i j k l m n o p q r s t "Shulgin's Sulfur Symphony – Part I". countyourculture. 15 January 2011. Archived from the original on 19 September 2019. Retrieved 22 October 2017.
  16. ^ Daniel Trachsel (2003). "Synthesis of novel (phenylalkyl)amines for the investigation of structure-activity relationships. Part 2. 4-Thio-substituted [2-(2,5-dimethoxyphenyl)ethyl]amines (=2,5-dimethoxybenzeneethanamines)". Helvetica Chimica Acta. 86 (7): 2610–2619. doi:10.1002/hlca.200390210.
  17. ^ Varty GB, Canal CE, Mueller TA, Hartsel JA, Tyagi R, Avery K, Morgan ME, Reichelt AC, Pathare P, Stang E, Palfreyman MG, Nivorozhkin A. Synthesis and Structure-Activity Relationships of 2,5-Dimethoxy-4-Substituted Phenethylamines and the Discovery of CYB210010: A Potent, Orally Bioavailable and Long-Acting Serotonin 5-HT2 Receptor Agonist. J Med Chem. 2024 Apr 25;67(8):6144-6188. doi:10.1021/acs.jmedchem.3c01961 PMID 38593423
  18. ^ Daniel Trachsel; David Lehmann & Christoph Enzensperger (2013). Phenethylamine: Von der Struktur zur Funktion. Nachtschatten Verlag AG. ISBN 978-3-03788-700-4.
  19. ^ Kruegel AC. Phenalkylamines and Methods of Treating Mood Disorders. Patent WO 2022/006186
  20. ^ "Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". Canada Gazette. April 15, 2016. Retrieved August 28, 2016.