Chemistry:25I-NBOH

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25I-NBOH (NBOH-2C-I, Cimbi-27, 2C-I-NBOH) is a derivative of the phenethylamine-derived hallucinogen 2C-I that was discovered in 2006 by a team at Purdue University. It is a known metabolite of 25I-NBOMe[1][2] and has also been encountered as a novel designer drug.[2][3]

Use and effects

The dose range of 25I-NBOH is 300 to 1,000 μg, with an estimated typical dose of 700 μg.[4][3] The route of administration is sublingual or buccal.[4]

Interactions

Pharmacology

Pharmacodynamics

25I-NBOH activities
Target Affinity (Ki, nM)
5-HT1A 2,220–>10,000 (Ki)
37,000 (EC50)
74% (Emax)
5-HT1B 2,446
5-HT1D 1,277
5-HT1E >10,000
5-HT1F ND
5-HT2A 0.061–1.12 (Ki)
0.074–1.52 (EC50)
86–136% (Emax)
5-HT2B 1.9–2.8 (Ki)
111 (EC50)
21% (Emax)
5-HT2C 0.13–1.4 (Ki)
2.4–32 (EC50)
94–101% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A 965
5-HT6 111
5-HT7 3,472
α1A 3,924
α1B >10,000
α1D >10,000
α2A 2,257
α2B 3,043
α2C 1,003
β1 1,088
β2, β3 ND
D1 ND
D2 >10,000
D3 678
D4 844
D5 >10,000
H1, H2 ND
H3 >10,000
H4 ND
M1–M5 >10,000
I1 ND
σ1 160
σ2 264
MOR 47 (Ki)
1,330–23,400 (EC50)
16–55% (Emax)
DOR ND
KOR 328
TAAR1 ND
SERT 1,155–1,220 (Ki)
1,720 (IC50)
Inactive (EC50)
NET 4,060 (Ki)
629 (IC50)
Inactive (EC50)
DAT 8,500 (Ki)
30,700 (IC50)
Inactive (EC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [5][6][7][8][9][10][11]
[12][1][13][14][15][16]

25I-NBOH acts as a potent agonist of the 5-HT2A receptor,[17][18] with a Ki of 0.061 nM at the human 5-HT2A receptor, similar to the better-known compound 25I-NBOMe, making it some twelve times the potency of 2C-I itself.

Although in vitro tests show this compound acts as an agonist, animal studies to confirm these findings have not been reported. While the N-benzyl derivatives of 2C-I had significantly increased binding to 5-HT2A receptor fragments, compared to 2C-I, the N-benzyl derivatives of DOI, such as DOI-NBOMe, were less active compared to DOI.[19]

25I-NBOH is notable in having been found to be one of the most selective agonists of the serotonin 5-HT2A receptor known, with an EC50 value of 0.074 nM and with more than 400-fold selectivity over the serotonin 5-HT2C receptor.[15][11] However, in another study, it only had about 6-fold selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor.[13]

25I-NBOH produces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents.[4]

Chemistry

Analysis

25I-NBOH is a labile molecule which fragments into 2C-I when analyzed by routine gas chromatography (GC) methods.[20] A specific method for reliable identification of 25I-NBOH using GC/MS has been reported, allowing forensic forces worldwide to correctly identify this compound.[21]

Analogues

Analogues of 25I-NBOH include 2C-I, DOI, 25B-NBOH, 25C-NBOH, 25I-NBOMe, 25I-NB3OMe, 25I-NBMD, 25I-NB4OMe, 25I-NB34MD, 25I-NBF, and DOI-NBOMe, among others.

History

25I-NBOH was first described in the scientific literature by Ralm Heim and colleagues by 2000.[22][23][24]

Society and culture

Canada

25I-NBOH is a controlled substance in Canada under phenethylamine blanket-ban language.[25]

Sweden

The Riksdag added 25I-NBOH to Narcotic Drugs Punishments Act under Swedish schedule I ("substances, plant materials and fungi which normally do not have medical use") as of August 18, 2015, published by Medical Products Agency MPA) in regulation HSLF-FS 2015:12 listed as "25I-NBOH" and "2-([2-(4-jodo-2,5-dimetoxifenyl)etylamino]metyl)fenol".[26]

United Kingdom

This substance is a Class A drug in the United Kingdom as a result of the N-benzylphenethylamine catch-all clause in the Misuse of Drugs Act 1971.[27]


United States

25I-NBOH is not an explicitly controlled substance in the United States.[28] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

See also

References

  1. ↑ 1.0 1.1 "Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens". Current Topics in Behavioral Neurosciences 32: 283–311. 2017. doi:10.1007/7854_2016_64. ISBN 978-3-319-52442-9. PMID 28097528. 
  2. ↑ 2.0 2.1 "25X-NBOMe compounds - chemistry, pharmacology and toxicology. A comprehensive review". Critical Reviews in Toxicology 53 (1): 15–33. January 2023. doi:10.1080/10408444.2023.2194907. PMID 37115704. 
  3. ↑ 3.0 3.1 "25I-NBOH: a new potent serotonin 5-HT2A receptor agonist identified in blotter paper seizures in Brazil". Forensic Toxicology 35 (2): 408–414. 2017. doi:10.1007/s11419-017-0357-x. PMID 28706567. 
  4. ↑ 4.0 4.1 4.2 "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology 167. May 2020. doi:10.1016/j.neuropharm.2019.107933. PMID 31917152. PMC 9191653. http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf. 
  5. ↑ "Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists". Molecular Pharmacology 70 (6): 1956–1964. December 2006. doi:10.1124/mol.106.028720. PMID 17000863. 
  6. ↑ Braden MR (2007). Towards a biophysical understanding of hallucinogen action (Ph.D. thesis). Purdue University. ProQuest 304838368.
  7. ↑ Ettrup, A. (2010). Serotonin receptor studies in the pig brain: pharmacological intervention and positron emission tomography tracer development (Doctoral dissertation, Faculty of Health Sciences, University of Copenhagen). https://research.regionh.dk/en/publications/serotonin-receptor-studies-in-the-pig-brain-pharmacological-inter
  8. ↑ Hansen M (2010-12-16). Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain (Ph.D. thesis). University of Copenhagen. doi:10.13140/RG.2.2.33671.14245.
  9. ↑ "Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers". European Journal of Nuclear Medicine and Molecular Imaging 38 (4): 681–693. April 2011. doi:10.1007/s00259-010-1686-8. PMID 21174090. 
  10. ↑ "Structure–activity relationships of serotonin 5-HT 2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling 1 (5): 559–579. 2012. doi:10.1002/wmts.42. ISSN 2190-460X. 
  11. ↑ 11.0 11.1 "Synthesis and Structure–Activity Relationships of N -Benzyl Phenethylamines as 5-HT 2A/2C Agonists". ACS Chemical Neuroscience 5 (3): 243–249. 19 March 2014. doi:10.1021/cn400216u. ISSN 1948-7193. PMID 24397362. 
  12. ↑ "Chemistry and Structure-Activity Relationships of Psychedelics". Current Topics in Behavioral Neurosciences 36: 1–43. 2018. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. 
  13. ↑ 13.0 13.1 "Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors". Biochemical Pharmacology 158: 27–34. December 2018. doi:10.1016/j.bcp.2018.09.024. PMID 30261175. 
  14. ↑ "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor". Archives of Toxicology 94 (10): 3449–3460. October 2020. doi:10.1007/s00204-020-02836-w. PMID 32627074. Bibcode: 2020ArTox..94.3449P. 
  15. ↑ 15.0 15.1 "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews 124 (1): 124–163. January 2024. doi:10.1021/acs.chemrev.3c00375. PMID 38033123. "Hansen et al. reported that the introduction of a 2-hydroxyl group on the benzyl substitution led to compounds with very high affinity for 5-HT2AR as well as good selectivity, known as the 25X-NBOH compounds.176 Besides the above-mentioned compound 25CN-NBOH (104), other substituents also provided excellent 5-HT2AR agonists with great selectivity. For example, 25I-NBOH (145) showed high affinity (pKi = 9.15, [ 3 H]-ketanserin) and potent agonism (pEC50 = 10.13, PIhydrolysis) at 5-HT2AR, with 100- and over 400-fold binding and selectivity against 5-HT2CR, respectively.176". 
  16. ↑ "Off-target activity of NBOMes and NBOMe analogs at the µ opioid receptor". Archives of Toxicology 97 (5): 1367–1384. May 2023. doi:10.1007/s00204-023-03465-9. PMID 36853332. Bibcode: 2023ArTox..97.1367D. 
  17. ↑ "Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers". European Journal of Nuclear Medicine and Molecular Imaging 38 (4): 681–693. April 2011. doi:10.1007/s00259-010-1686-8. PMID 21174090. 
  18. ↑ "Theoretical studies on the interaction of partial agonists with the 5-HT2A receptor". Journal of Computer-aided Molecular Design 25 (1): 51–66. January 2011. doi:10.1007/s10822-010-9400-2. PMID 21088982. Bibcode: 2011JCAMD..25...51S. 
  19. ↑ "Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists". Molecular Pharmacology 70 (6): 1956–1964. December 2006. doi:10.1124/mol.106.028720. PMID 17000863. 
  20. ↑ "2A receptor agonist identified in blotter paper seizures in Brazil". Forensic Toxicology 35 (2): 408–414. 2017. doi:10.1007/s11419-017-0357-x. PMID 28706567. 
  21. ↑ "Preventing misidentification of 25I-NBOH as 2C-I on routine GC–MS analyses". Forensic Toxicology 35 (2): 415–420. 2017. doi:10.1007/s11419-017-0362-0. http://eprints.lincoln.ac.uk/26957/7/25i-nboh%20aceito.pdf. 
  22. ↑ "39. Novel Extremely Potent Partial 5-HT2A-Receptor Agonists: Successful Application of a New Structure-Activity Concept". Arch. Pharm. Pharm. Med. Chem 333 (Suppl 1): 1–40 (18). March 2000. ISSN 0365-6233. https://scholar.google.com/scholar?cluster=5753981208249154444. 
  23. ↑ "B 1.11. N-Benzylated phenylethanamines are highly potent partial agonists at 5-HT2A receptors". Arch. Pharm. Pharm. Med. Chem 333 (Suppl 2): 1–84 (30). 2000. https://scholar.google.com/scholar?cluster=18169232060279208950. 
  24. ↑ "Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts." (in German). diss.fu-berlin.de. 25 March 2003. http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000001221. 
  25. ↑ "Controlled Drugs and Substances Act". https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 
  26. ↑ "Gemensamma författningssamlingen avseende hälso- och sjukvård, socialtjänst, läkeme del, folkhälsa m.m.". Lakemedelsverket. https://lakemedelsverket.se/upload/lvfs/HSLF_FS_2015_12.pdf. 
  27. ↑ "The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014" (in en). http://www.legislation.gov.uk/uksi/2014/1106/made. 
  28. ↑ Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026, https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf 




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