:2C-H

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{{Infobox drug

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| image = 2C-H-Chemdraw.png

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| image2 = 2C-H-3d-sticks.png

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| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 3600-86-0

| CAS_supplemental =
3166-74-3 (hydrochloride)

| PubChem = 76632

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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 69096

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| UNII = 9A8XF4GA0X

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| ChEBI = 125507

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 287047

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| synonyms = 2,5-Dimethoxyphenethylamine; 2,5-DMPEA

| IUPAC_name = 2-(2,5-dimethoxyphenyl)ethanamine

| C=10 | H=15 | N=1 | O=2

| SMILES = COC1=CC(=C(C=C1)OC)CCN

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C10H15NO2/c1-12-9-3-4-10(13-2)8(7-9)5-6-11/h3-4,7H,5-6,11H2,1-2H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = WNCUVUUEJZEATP-UHFFFAOYSA-N

| melting_point = 138

| melting_high = 139

| melting_notes = (hydrochloride)

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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.{{CitePiHKAL}} [https://www.erowid.org/library/books_online/pihkal/pihkal032.shtml 2C-H Entry in PiHKAL] In the book PiHKAL, Alexander Shulgin lists both the dosage and duration of 2C-H effects as unknown. Very little data exists about the pharmacological properties, metabolism, and toxicity of 2C-H.

Pharmacology

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|+ {{Nowrap|2C-H activities}}

TargetAffinity (Ki, nM)
5-HT1A70
5-HT1B{{Abbr|ND|No data}}
5-HT1D{{Abbr|ND|No data}}
5-HT1E{{Abbr|ND|No data}}
5-HT1F{{Abbr|ND|No data}}
5-HT2A1,600–3,000 (Ki)
2,408–>10,000 ({{Abbrlink|EC50|half-maximal effective concentration}})
17,800 ({{Abbrlink|IC50|half-maximal inhibitory concentration}})
0–78% ({{Abbrlink|Emax|maximal efficacy}})
5-HT2B6,200 ({{Abbr|EC50|half-maximal effective concentration}})
46% ({{Abbr|Emax|maximal efficacy}})
5-HT2C4,100–5,520 (Ki)
1,175–3,967 ({{Abbr|EC50|half-maximal effective concentration}})
76% ({{Abbr|Emax|maximal efficacy}})
5-HT3{{Abbr|ND|No data}}
5-HT4{{Abbr|ND|No data}}
5-HT5A{{Abbr|ND|No data}}
5-HT6{{Abbr|ND|No data}}
5-HT7{{Abbr|ND|No data}}
α1A7,900 (Ki)
11,000 ({{Abbr|EC50|half-maximal effective concentration}})
α1B, α1D{{Abbr|ND|No data}}
α2A1,000
α2B, α2C{{Abbr|ND|No data}}
β1β3{{Abbr|ND|No data}}
D1>14,000
D29,000
D3>17,000
D4, D5{{Abbr|ND|No data}}
H1>25,000
{{Abbrlink|TAAR1|Trace amine-associated receptor 1}}11,000 (Ki) (mouse)
900 (Ki) (rat)
7,500 ({{Abbr|EC50|half-maximal effective concentration}}) (mouse)
1,500 ({{Abbr|EC50|half-maximal effective concentration}}) (rat)
2,010–6,500 ({{Abbr|EC50|half-maximal effective concentration}}) (human)
56% ({{Abbr|Emax|maximal efficacy}}) (mouse)
80% ({{Abbr|Emax|maximal efficacy}}) (rat)
53–69% ({{Abbr|Emax|maximal efficacy}}) (human)
{{Abbrlink|SERT|Serotonin transporter}}>30,000 (Ki)
311,000 ({{Abbr|IC50|half-maximal inhibitory concentration}})
{{Abbr|ND|No data}} ({{Abbr|EC50|half-maximal effective concentration}})
{{Abbrlink|NET|Norepinephrine transporter}}>30,000 (Ki)
125,000 ({{Abbr|IC50|half-maximal inhibitory concentration}})
{{Abbr|ND|No data}} ({{Abbr|EC50|half-maximal effective concentration}})
{{Abbrlink|DAT|Dopamine transporter}}>30,000 (Ki)
857,000 ({{Abbr|IC50|half-maximal inhibitory concentration}})
{{Abbr|ND|No data}} ({{Abbr|EC50|half-maximal effective concentration}})
{{Abbrlink|MAO-A|Monoamine oxidase A}}{{Abbr|ND|No data}} ({{Abbr|IC50|half-maximal inhibitory concentration}})
{{Abbrlink|MAO-B|Monoamine oxidase B}}1,700 ({{Abbr|IC50|half-maximal inhibitory concentration}})
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| colspan="2" style="width: 1px; background-color:#eaecf0; text-align: center;" | Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: {{cite web | title=Kᵢ Database | website=PDSP | date=16 March 2025 | url=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= | access-date=16 March 2025}}{{cite web | last=Liu | first=Tiqing | title=BindingDB BDBM50026778 2-(2,5-Dimethoxy-phenyl)-ethylamine::2-(2,5-dimethoxyphenyl)ethylamine::CHEMBL287047 | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50026778 | access-date=16 March 2025}}{{cite journal | vauthors = Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) | journal = Neuropharmacology | volume = 99 | issue = | pages = 546–553 | date = December 2015 | pmid = 26318099 | doi = 10.1016/j.neuropharm.2015.08.034 | url = 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}}{{cite journal | vauthors = Rudin D, Luethi D, Hoener MC, Liechti ME | title=Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues | journal=The FASEB Journal | volume=36 | issue=S1 | date=2022 | issn=0892-6638 | doi=10.1096/fasebj.2022.36.S1.R2121 | doi-access=free | url=https://www.researchgate.net/publication/360423277_Structure-activity_relation_of_halogenated_25-dimethoxyamphetamines_compared_to_their_a-desmethyl_2C_analogues}}{{cite journal | vauthors = Pottie E, Cannaert A, Stove CP | title = In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor | journal = Arch Toxicol | volume = 94 | issue = 10 | pages = 3449–3460 | date = October 2020 | pmid = 32627074 | doi = 10.1007/s00204-020-02836-w | bibcode = 2020ArTox..94.3449P | url = | hdl = 1854/LU-8687071 | hdl-access = free }}{{cite journal | vauthors = Villalobos CA, Bull P, Sáez P, Cassels BK, Huidobro-Toro JP | title = 4-Bromo-2,5-dimethoxyphenethylamine (2C-B) and structurally related phenylethylamines are potent 5-HT2A receptor antagonists in Xenopus laevis oocytes | journal = Br J Pharmacol | volume = 141 | issue = 7 | pages = 1167–1174 | date = April 2004 | pmid = 15006903 | pmc = 1574890 | doi = 10.1038/sj.bjp.0705722 | url = }}{{cite journal | vauthors = Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP | title = Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors | journal = J Pharmacol Exp Ther | volume = 321 | issue = 3 | pages = 1054–1061 | date = June 2007 | pmid = 17337633 | doi = 10.1124/jpet.106.117507 | url = }}{{cite journal | vauthors = Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, Glennon RA | title = 1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists | journal = J Med Chem | volume = 43 | issue = 16 | pages = 3074–3084 | date = August 2000 | pmid = 10956215 | doi = 10.1021/jm9906062 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=ad45346022bb7e6e1bec1fbfbcca3bcb60b13058| url-access = subscription }}{{cite journal | vauthors = DeMarinis RM, Bryan WM, Shah DH, Hieble JP, Pendleton RG | title = Alpha-adrenergic agents. 1. Direct-acting alpha 1 agonists related to methoxamine | journal = J Med Chem | volume = 24 | issue = 12 | pages = 1432–1437 | date = December 1981 | pmid = 6118438 | doi = 10.1021/jm00144a012 | url = }}{{cite journal | vauthors = Wagmann L, Brandt SD, Stratford A, Maurer HH, Meyer MR | title = Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases | journal = Drug Test Anal | volume = 11 | issue = 2 | pages = 318–324 | date = February 2019 | pmid = 30188017 | doi = 10.1002/dta.2494 | url = }}{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = https://web.archive.org/web/20250509235235/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}}{{cite journal | vauthors = Lewin AH, Navarro HA, Mascarella SW | title = Structure-activity correlations for beta-phenethylamines at human trace amine receptor 1 | journal = Bioorg Med Chem | volume = 16 | issue = 15 | pages = 7415–7423 | date = August 2008 | pmid = 18602830 | pmc = 2601700 | doi = 10.1016/j.bmc.2008.06.009 | url = }}

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. It also shows affinity for the serotonin 5-HT1A receptor, higher than that of any other 2C drug. The drug exhibits agonist activity in vitro at the human trace amine associated receptor 1 (TAAR1).{{cite web|title="PubChem"|url=https://pubchem.ncbi.nlm.nih.gov/compound/76632#section=BioAssay-Results}}

2C-H produces visual and auditory changes in rodents, but is much less potent than other 2C drugs.{{cite journal | vauthors = Tirri M, Bilel S, Arfè R, Corli G, Marchetti B, Bernardi T, Boccuto F, Serpelloni G, Botrè F, De-Giorgio F, Golembiowska K, Marti M | title = 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 | journal = Front Psychiatry | volume = 13 | issue = | pages = 875722 | date = 2022 | pmid = 35530025 | pmc = 9069068 | doi = 10.3389/fpsyt.2022.875722 | doi-access = free | url = }} It also produces hypolocomotion at high doses similarly to other psychedelics, but failed to affect prepulse inhibition in contrast to other psychedelics. The drug shows highly potent and fully efficacious anti-inflammatory effects.{{cite journal | vauthors = Nichols CD | title = Psychedelics as potent anti-inflammatory therapeutics | journal = Neuropharmacology | volume = 219 | issue = | pages = 109232 | date = November 2022 | pmid = 36007854 | doi = 10.1016/j.neuropharm.2022.109232 | url = | doi-access = free }}{{cite book | vauthors = Flanagan TW, Nichols CD | title = Disruptive Psychopharmacology | chapter = Psychedelics and Anti-inflammatory Activity in Animal Models | series = Curr Top Behav Neurosci | volume = 56 | pages = 229–245 | date = 2022 | pmid = 35546383 | doi = 10.1007/7854_2022_367 | isbn = 978-3-031-12183-8 | chapter-url = }}{{cite journal | vauthors = Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD | title = Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore | journal = ACS Pharmacol Transl Sci | volume = 4 | issue = 2 | pages = 488–502 | date = April 2021 | pmid = 33860179 | pmc = 8033619 | doi = 10.1021/acsptsci.0c00063 | url = }}

Chemistry

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

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.

History

2C-H was first synthesized in 1932 by Johannes S. Buck.{{cite journal| vauthors = Buck JS |title=Hydroxy- and Dihydroxyphenylethylmethylamines and their Ether|journal=Journal of the Chemical Society|date=1932|volume=54|issue=9|pages=3661–3665|doi=10.1021/ja01348a024}}

Legal status

=Canada=

As of October 31, 2016; 2C-H is a controlled substance (Schedule III) in Canada.{{Cite web|url=http://gazette.gc.ca/rp-pr/p2/2016/2016-05-04/html/sor-dors72-eng.php|title=Canada Gazette – Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)|date=4 May 2016}}

= 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.{{cite web |title=Rules - 2013 - Establishment of Drug Codes for 26 Substances (SDAPA) |url= http://www.deadiversion.usdoj.gov/fed_regs/rules/2013/fr0104.htm |publisher=U.S. Department of Justice |access-date=22 July 2012|archive-date= 22 March 2015 |archive-url= https://web.archive.org/web/20150322225248/http://www.deadiversion.usdoj.gov/fed_regs/rules/2013/fr0104.htm |url-status=dead}} 2C-H's DEA Drug Code is 7517.

See also

References

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