Chemistry:2C-H

From HandWiki

2C-H, also known as 2,5-dimethoxyphenethylamine (2,5-DMPEA) or as DMPEA-4, 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 ND
5-HT1D ND
5-HT1E ND
5-HT1F ND
5-HT2A 1,600–3,000 (Ki)
2,408–>10,000 (EC50)
17,800 (IC50)
0–78% (Emax)
5-HT2B 6,200 (EC50)
46% (Emax)
5-HT2C 4,100–5,520 (Ki)
1,175–3,967 (EC50)
76% (Emax)
5-HT3 ND
5-HT4 ND
5-HT5A ND
5-HT6 ND
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
TAAR1 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)
SERT >30,000 (Ki)
311,000 (IC50)
ND (EC50)
NET >30,000 (Ki)
125,000 (IC50)
ND (EC50)
DAT >30,000 (Ki)
857,000 (IC50)
ND (EC50)
MAO-A ND (IC50)
MAO-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][14]

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][6][8][9] 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).[15]

2C-H produces visual and auditory changes in rodents, but is much less potent than other 2C drugs.[16] It also produces hypolocomotion at high doses similarly to other psychedelics, but failed to affect prepulse inhibition in contrast to other psychedelics.[16] The drug shows highly potent and fully efficacious anti-inflammatory effects.[17][18][9]

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.[6]

History

2C-H was first synthesized in 1932 by Johannes S. Buck.[19]

Society and culture

Canada

As of October 31, 2016; 2C-H is a controlled substance (Schedule III) in Canada.[20]

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.[21] 2C-H's DEA Drug Code is 7517.

See also

References

  1. ↑ 1.0 1.1 1.2 Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. http://www.erowid.org/library/books_online/pihkal/pihkal.shtml.  2C-H Entry in PiHKAL
  2. ↑ "Kᵢ Database". 16 March 2025. https://pdsp.unc.edu/kidb2/kidb/web/kis-results/index?KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14672&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D=. 
  3. ↑ Liu, Tiqing. "BindingDB BDBM50026778 2-(2,5-Dimethoxy-phenyl)-ethylamine::2-(2,5-dimethoxyphenyl)ethylamine::CHEMBL287047". https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50026778. 
  4. ↑ 4.0 4.1 4.2 "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)". Neuropharmacology 99: 546–553. December 2015. doi:10.1016/j.neuropharm.2015.08.034. PMID 26318099. https://psilosybiini.info/paperit/Receptor%20interaction%20profiles%20of%20novel%20N-2-methoxybenzyl%20(NBOMe)%20derivatives%20of%202,5-dimethoxy-substituted%20phenethylamines%20(2C%20drugs)%20(Rickli%20et%20al.,%202015).pdf. 
  5. ↑ "Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues". The FASEB Journal 36 (S1). 2022. doi:10.1096/fasebj.2022.36.S1.R2121. ISSN 0892-6638. https://www.researchgate.net/publication/360423277. 
  6. ↑ 6.0 6.1 6.2 "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. October 2020. doi:10.1007/s00204-020-02836-w. PMID 32627074. Bibcode: 2020ArTox..94.3449P. 
  7. ↑ "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. April 2004. doi:10.1038/sj.bjp.0705722. PMID 15006903. 
  8. ↑ 8.0 8.1 "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. June 2007. doi:10.1124/jpet.106.117507. PMID 17337633. 
  9. ↑ 9.0 9.1 9.2 "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. April 2021. doi:10.1021/acsptsci.0c00063. PMID 33860179. 
  10. ↑ "1-[4-(3-Phenylalkyl)phenyl-2-aminopropanes as 5-HT(2A) partial agonists"]. J Med Chem 43 (16): 3074–3084. August 2000. doi:10.1021/jm9906062. PMID 10956215. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=ad45346022bb7e6e1bec1fbfbcca3bcb60b13058. 
  11. ↑ "Alpha-adrenergic agents. 1. Direct-acting alpha 1 agonists related to methoxamine". J Med Chem 24 (12): 1432–1437. December 1981. doi:10.1021/jm00144a012. PMID 6118438. 
  12. ↑ "Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases". Drug Test Anal 11 (2): 318–324. February 2019. doi:10.1002/dta.2494. PMID 30188017. 
  13. ↑ "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1". J Pharmacol Exp Ther 357 (1): 134–144. April 2016. doi:10.1124/jpet.115.229765. PMID 26791601. https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA. 
  14. ↑ "Structure-activity correlations for beta-phenethylamines at human trace amine receptor 1". Bioorg Med Chem 16 (15): 7415–7423. August 2008. doi:10.1016/j.bmc.2008.06.009. PMID 18602830. 
  15. ↑ ""PubChem"". https://pubchem.ncbi.nlm.nih.gov/compound/76632#section=BioAssay-Results. 
  16. ↑ 16.0 16.1 "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. 2022. doi:10.3389/fpsyt.2022.875722. PMID 35530025. 
  17. ↑ "Psychedelics as potent anti-inflammatory therapeutics". Neuropharmacology 219. November 2022. doi:10.1016/j.neuropharm.2022.109232. PMID 36007854. 
  18. ↑ "Psychedelics and Anti-inflammatory Activity in Animal Models". Disruptive Psychopharmacology. Curr Top Behav Neurosci. 56. 2022. pp. 229–245. doi:10.1007/7854_2022_367. ISBN 978-3-031-12183-8. 
  19. ↑ "Hydroxy- and Dihydroxyphenylethylmethylamines and their Ether". Journal of the Chemical Society 54 (9): 3661–3665. 1932. doi:10.1021/ja01348a024. 
  20. ↑ "Canada Gazette – Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". 4 May 2016. http://gazette.gc.ca/rp-pr/p2/2016/2016-05-04/html/sor-dors72-eng.php. 
  21. ↑ "Rules - 2013 - Establishment of Drug Codes for 26 Substances (SDAPA)". U.S. Department of Justice. http://www.deadiversion.usdoj.gov/fed_regs/rules/2013/fr0104.htm. 

Template:Psychedelics

Template:Chemical classes of psychoactive drugs



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:2C-H&oldid=4032757"