2C-H, also known as 2,5-dimethoxyphenethylamine (2,5-DMPEA), is a lesser-known drug of the phenethylamine and 2C (4-substituted 2,5-dimethoxyphenethylamine) families. It is the parent compound of the 2C drugs.

Use and effects

There is no record of 2C-H trials in humans, as it would likely be destroyed by monoamine oxidase enzymes before causing any significant psychoactive effects.[1] In the book PiHKAL, Alexander Shulgin lists both the dosage and duration of 2C-H effects as unknown.[1] Very little data exists about the pharmacological properties, metabolism, and toxicity of 2C-H.

Pharmacology

2C-H activities
Target Affinity (Ki, nM)
5-HT1A 70
5-HT1B–5-HT1F ND
5-HT2A 1,600–3,000 (Ki)
2,408–>10,000 (EC50Tooltip half-maximal effective concentration)
17,800 (IC50Tooltip half-maximal inhibitory concentration)
0–78% (EmaxTooltip maximal efficacy)
5-HT2B 6,200 (EC50)
46% (Emax)
5-HT2C 4,100–5,520 (Ki)
1,175–3,967 (EC50)
76% (Emax)
5-HT3–5-HT7 ND
α1A 7,900 (Ki)
11,000 (EC50)
α1B, α1D ND
α2A 1,000
α2B, α2C ND
β1–β3 ND
D1 >14,000
D2 9,000
D3 >17,000
D4, D5 ND
H1 >25,000
TAAR1Tooltip Trace amine-associated receptor 1 11,000 (Ki) (mouse)
900 (Ki) (rat)
7,500 (EC50) (mouse)
1,500 (EC50) (rat)
2,010–6,500 (EC50) (human)
56% (Emax) (mouse)
80% (Emax) (rat)
53–69% (Emax) (human)
SERTTooltip Serotonin transporter >30,000 (Ki)
311,000 (IC50)
ND (EC50)
NETTooltip Norepinephrine transporter >30,000 (Ki)
125,000 (IC50)
ND (EC50)
DATTooltip Dopamine transporter >30,000 (Ki)
857,000 (IC50)
ND (EC50)
MAO-ATooltip Monoamine oxidase A ND (IC50)
MAO-BTooltip Monoamine oxidase B 1,700 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [2][3][4][5][6][7][8][9][10][11][12][13]

2C-H acts as a partial agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors, albeit with far lower potency than other 2C drugs.[4][5][7][8] It also shows affinity for the serotonin 5-HT1A receptor, higher than that of any other 2C drug.[4] The drug exhibits agonist activity in vitro at the human trace amine associated receptor 1 (TAAR1).[14]

2C-H produces visual and auditory changes in rodents, but is much less potent than other 2C drugs.[15] It also produces hypolocomotion at high doses similarly to other psychedelics, but failed to affect prepulse inhibition in contrast to other psychedelics.[15] The drug shows highly potent and fully efficacious anti-inflammatory effects.[16][17][8]

Chemistry

2C-H is used as a precursor in the synthesis of other phenethylamines such as 2C-B, 2C-I, and 2C-N.[1]

The N-methyl derivative of 2C-H, N-methyl-2C-H, has reduced activational potency and efficacy at the serotonin 5-HT2A receptor compared to 2C-H.[5]

History

2C-H was first synthesized in 1932 by Johannes S. Buck.[18]

Canada

As of October 31, 2016; 2C-H is a controlled substance (Schedule III) in Canada.[19]

United States

As of July 9, 2012, 2C-H is a Schedule I controlled substance in the United States, under the Synthetic Drug Abuse Prevention Act of 2012.[20] 2C-H's DEA Drug Code is 7517.

References

  1. ^ a b c Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. 2C-H Entry in PiHKAL
  2. ^ "Kᵢ Database". PDSP. 16 March 2025. Retrieved 16 March 2025.
  3. ^ Liu T. "BindingDB BDBM50026778 2-(2,5-Dimethoxy-phenyl)-ethylamine::2-(2,5-dimethoxyphenyl)ethylamine::CHEMBL287047". BindingDB. Retrieved 16 March 2025.
  4. ^ a b c 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.
  5. ^ a b c 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.
  6. ^ Villalobos CA, Bull P, Sáez P, Cassels BK, Huidobro-Toro JP (April 2004). "4-Bromo-2,5-dimethoxyphenethylamine (2C-B) and structurally related phenylethylamines are potent 5-HT2A receptor antagonists in Xenopus laevis oocytes". Br J Pharmacol. 141 (7): 1167–1174. doi:10.1038/sj.bjp.0705722. PMC 1574890. PMID 15006903.
  7. ^ a b 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". J Pharmacol Exp Ther. 321 (3): 1054–1061. doi:10.1124/jpet.106.117507. PMID 17337633.
  8. ^ a b c 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.
  9. ^ Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, et al. (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.
  10. ^ DeMarinis RM, Bryan WM, Shah DH, Hieble JP, Pendleton RG (December 1981). "Alpha-adrenergic agents. 1. Direct-acting alpha 1 agonists related to methoxamine". J Med Chem. 24 (12): 1432–1437. doi:10.1021/jm00144a012. PMID 6118438.
  11. ^ 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.
  12. ^ 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". J Pharmacol Exp Ther. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID 26791601.
  13. ^ Lewin AH, Navarro HA, Mascarella SW (August 2008). "Structure-activity correlations for beta-phenethylamines at human trace amine receptor 1". Bioorg Med Chem. 16 (15): 7415–7423. doi:10.1016/j.bmc.2008.06.009. PMC 2601700. PMID 18602830.
  14. ^ ""PubChem"".
  15. ^ a b Tirri M, Bilel S, Arfè R, Corli G, Marchetti B, Bernardi T, et al. (2022). "Effect of -NBOMe Compounds on Sensorimotor, Motor, and Prepulse Inhibition Responses in Mice in Comparison With the 2C Analogs and Lysergic Acid Diethylamide: From Preclinical Evidence to Forensic Implication in Driving Under the Influence of Drugs". Front Psychiatry. 13: 875722. doi:10.3389/fpsyt.2022.875722. PMC 9069068. PMID 35530025.
  16. ^ Nichols CD (November 2022). "Psychedelics as potent anti-inflammatory therapeutics". Neuropharmacology. 219: 109232. doi:10.1016/j.neuropharm.2022.109232. PMID 36007854.
  17. ^ Flanagan TW, Nichols CD (2022). "Psychedelics and Anti-inflammatory Activity in Animal Models". Disruptive Psychopharmacology. Curr Top Behav Neurosci. Vol. 56. pp. 229–245. doi:10.1007/7854_2022_367. ISBN 978-3-031-12183-8. PMID 35546383.
  18. ^ Buck JS (1932). "Hydroxy- and Dihydroxyphenylethylmethylamines and their Ether". Journal of the Chemical Society. 54 (9): 3661–3665. doi:10.1021/ja01348a024.
  19. ^ "Canada Gazette – Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". 4 May 2016.
  20. ^ "Rules - 2013 - Establishment of Drug Codes for 26 Substances (SDAPA)". U.S. Department of Justice. Archived from the original on 22 March 2015. Retrieved 22 July 2012.
Allikas: https://en.wikipedia.org/wiki/2C-H
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