2C-I

Last updated

2C-I
2C-I2DACS.svg
2C-I-3d-sticks.png
Clinical data
Other names4-Iodo-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-iodophenethylamine; 25I; Cimbi-88
Legal status
Legal status
Identifiers
  • 2-(4-iodo-2,5-dimethoxyphenyl)ethan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.217.507 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C10H14INO2
Molar mass 307.131 g·mol−1
3D model (JSmol)
Melting point 246 °C (475 °F)
  • Ic1cc(OC)c(cc1OC)CCN
  • InChI=1S/C10H14INO2/c1-13-9-6-8(11)10(14-2)5-7(9)3-4-12/h5-6H,3-4,12H2,1-2H3 Yes check.svgY
  • Key:PQHQBRJAAZQXHL-UHFFFAOYSA-N Yes check.svgY
   (verify)

2C-I, also known as 2,5-dimethoxy-4-iodophenethylamine, is a phenethylamine of the 2C family with psychedelic effects. [1] It was first synthesized by Alexander Shulgin, and is described in Shulgin's book PiHKAL (1991).

Contents

The substance is consumed as a recreational drug, and is circulated in the drug market in a powder form. 2C-I is sometimes confused with other related chemical substances such as 25I-NBOMe (2C-I-NBOMe), nicknamed "Smiles" and "N-bomb" in the media. [2] [3] [4]

Use

In the early 2000s, 2C-I was sold in Dutch smart shops as a recreational drug after the drug 2C-B was banned. [5]

According to the US Drug Enforcement Administration, 2C-I is taken orally or snorted in a powder form. [6]

Interactions

2C-I is metabolized by the monoamine oxidase (MAO) enzymes MAO-A and MAO-B. [7] [8] Monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, moclobemide, and selegiline may potentiate the effects of 2C-I. [7] [8] [9] This may result in overdose and serious toxicity. [9] [7]

Pharmacology

Pharmacodynamics

2C-I activities
Target Affinity (Ki, nM)
5-HT1A 107–970 (Ki)
4,900 (EC50 Tooltip half-maximal effective concentration)
102% (Emax Tooltip maximal efficacy)
5-HT1B 56
5-HT1D 40
5-HT1E 131
5-HT1F ND
5-HT2A 3.5–9.3 (Ki)
1.48–513 (EC50)
17–93% (Emax)
5-HT2B 9.3 (Ki)
19.1–150 (EC50)
70–101% (Emax)
5-HT2C 9.3–40 (Ki)
0.46–537 (EC50)
44–107% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 ND
5-HT7 1,316
α1A 5,100–>10,000
α1B >10,000
α1D >10,000
α2A 70–305
α2B 608
α2C 315
β1 4,512
β2 >10,000
β3 ND
D1 13,000
D2 1,013–2,700
D3 989–5,000
D4 2,788
D5 >10,000
H1 6,100
H2 >10,000
H3 >10,000
M1 >10,000
M2 1,429
M3 950
M4 1,129
M5 2,151
I1 ND
σ1 >10,000
σ2 5,470
MOR 2,522
DOR ND
KOR >10,000
TAAR1 Tooltip Trace amine-associated receptor 13,300 (Ki) (mouse)
120 (Ki) (rat)
2,400 (EC50) (mouse)
190 (EC50) (rat)
>10,000 (EC50) (human)
51% (Emax) (mouse)
50% (Emax) (rat)
SERT Tooltip Serotonin transporter950–4,900 (Ki)
5,600–13,000 (IC50 Tooltip half-maximal inhibitory concentration)
IA (EC50)
NET Tooltip Norepinephrine transporter15,000 (Ki)
22,000 (IC50)
IA (EC50)
DAT Tooltip Dopamine transporter>30,000 (Ki)
126,000 (IC50)
IA (EC50)
MAO-A Tooltip Monoamine oxidase A125,000 (IC50)
MAO-B Tooltip Monoamine oxidase B55,000 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [10] [11] [12] [13] [14] [15]
[16] [17] [18] [19] [20] [21]

2C-I acts as a serotonin receptor agonist. It produces psychedelic effects via serotonin 5-HT2A receptor activation.

It is inactive as a monoamine releasing agent and shows negligible activity as a monoamine reuptake inhibitor. [12] [11]

2C-I is a highly potent anti-inflammatory drug similarly to various other serotonergic psychedelics. [19] However, 2C-I showed the highest anti-inflammatory potency of any other assessed drug in a large series in one study. [19] It was more potent than (R)-DOI in terms of anti-inflammatory activity. [19]

Chemistry

Analogues and derivatives

Society and culture

2C-I in powder form. 2C-I Powder.jpg
2C-I in powder form.

Australia

2C-I is a schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015). [22] A schedule 9 drug is outlined in the Poisons Act 1964 as "Substances 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 the CEO". [23]

Canada

As of October 31, 2016, 2C-I is a controlled substance (Schedule III) in Canada. [24]

European Union

In December 2003, the European Council issued a binding order compelling all European Union member states to ban 2C-I within three months. [25]

Finland

Illegal: scheduled in the "government decree on substances, preparations and plants considered to be narcotic drugs". [26]

Sweden

Sveriges riksdag added 2C-I to schedule I ("substances, plant materials and fungi which normally do not have medical use") as a narcotic on March 16, 2004, published by the Medical Products Agency in their regulation LVFS 2004:3. [27]

United Kingdom

In the United Kingdom, 2C-I is controlled as a Class A substance. [25]

United States

As of July 9, 2012, in the United States 2C-I is a Schedule I substance under the Synthetic Drug Abuse Prevention Act of 2012, making possession, distribution and manufacture illegal. [25] A previous bill, introduced in March 2011, that would have done the same passed the House of Representatives, but was not passed by the Senate. [28]

See also

References

  1. ↑ Bosak A, LoVecchio F, Levine M (June 2013). "Recurrent seizures and serotonin syndrome following "2C-I" ingestion". Journal of Medical Toxicology. 9 (2): 196–198. doi:10.1007/s13181-013-0287-x. PMC   3657032 . PMID   23378129.
  2. ↑ "25I-NBOMe (2C-I-NBOMe): Fatalities / Deaths".
  3. ↑ Weiss, Piper (September 20, 2012). 2C-I or 'Smiles': The New Killer Drug Every Parent Should Know About. Yahoo! News
  4. ↑ Mackin T (October 9, 2012). "Dangerous synthetic drug making its way across the country". Archived from the original on October 31, 2012. WISH-TV
  5. ↑ de Boer D, Gijzels MJ, Bosman IJ, Maes RA (May–June 1999). "More data about the new psychoactive drug 2C-B". Journal of Analytical Toxicology. 23 (3): 227–228. doi: 10.1093/jat/23.3.227 . PMID   10369336.
  6. ↑ Reuters (March 20, 2011). Synthetic drug, subject of proposed bans, kill teen.
  7. 1 2 3 Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM (June 2013). "2C or not 2C: phenethylamine designer drug review". J Med Toxicol. 9 (2): 172–178. doi:10.1007/s13181-013-0295-x. PMC   3657019 . PMID   23494844.
  8. 1 2 Theobald DS, Maurer HH (January 2007). "Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series)". Biochem Pharmacol. 73 (2): 287–297. doi:10.1016/j.bcp.2006.09.022. PMID   17067556.
  9. 1 2 Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC   10851641 . PMID   37982394.
  10. ↑ "Kᵢ Database". PDSP. 16 March 2025. Retrieved 16 March 2025.
  11. 1 2 Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME (December 2015). "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)" (PDF). Neuropharmacology. 99: 546–553. doi:10.1016/j.neuropharm.2015.08.034. PMID   26318099.
  12. 1 2 Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB (March 2014). "Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function". Psychopharmacology (Berl). 231 (5): 875–888. doi:10.1007/s00213-013-3303-6. PMC   3945162 . PMID   24142203.
  13. ↑ Ettrup A, Hansen M, Santini MA, Paine J, Gillings N, Palner M, et al. (April 2011). "Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers". Eur J Nucl Med Mol Imaging. 38 (4): 681–693. doi:10.1007/s00259-010-1686-8. PMID   21174090.
  14. ↑ Rudin D, Luethi D, Hoener MC, Liechti ME (2022). "Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues". The FASEB Journal. 36 (S1) fasebj.2022.36.S1.R2121. doi: 10.1096/fasebj.2022.36.S1.R2121 . ISSN   0892-6638.
  15. ↑ Pottie E, Cannaert A, Stove CP (October 2020). "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor". Arch Toxicol. 94 (10): 3449–3460. Bibcode:2020ArTox..94.3449P. doi:10.1007/s00204-020-02836-w. hdl: 1854/LU-8687071 . PMID   32627074.
  16. ↑ Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, et al. (December 2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nat Commun. 14 (1) 8221. doi:10.1038/s41467-023-44016-1. PMC   10724237 . PMID   38102107.
  17. ↑ Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP (June 2002). "Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors". Br J Pharmacol. 136 (4): 510–519. doi:10.1038/sj.bjp.0704747. PMC   1573376 . PMID   12055129.
  18. ↑ Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, et al. (June 2007). "Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors" (PDF). J Pharmacol Exp Ther. 321 (3): 1054–1061. doi:10.1124/jpet.106.117507. PMID   17337633.
  19. 1 2 3 4 Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC   8033619 . PMID   33860179.
  20. ↑ Wagmann L, Brandt SD, Stratford A, Maurer HH, Meyer MR (February 2019). "Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases". Drug Test Anal. 11 (2): 318–324. doi:10.1002/dta.2494. PMID   30188017.
  21. ↑ Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (April 2016). "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1" (PDF). J Pharmacol Exp Ther. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID   26791601. Archived from the original (PDF) on 9 May 2025.
  22. ↑ Poisons Standard October 2015
  23. ↑ "Poisons Act 1964" (PDF). Archived from the original (PDF) on 2015-12-22. Retrieved 2015-12-13.
  24. ↑ Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)
  25. 1 2 3 "Erowid 2C-I Vault : Legal Status".
  26. ↑ "Valtioneuvoston asetus huumausaineina pidettävistä aineista, valmisteista ja kasveista | 543/2008 | Lainsäädäntö | Finlex".
  27. ↑ "Läkemedelsverkets författningssamling" (PDF) (in Swedish).
  28. ↑ "H.R. 1254 (112th): Synthetic Drug Control Act of 2011". GovTrack. Retrieved 30 September 2015.
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