25I-NBOH

Last updated

25I-NBOH
2C-I-NBOH-skeletal.svg
Clinical data
Other namesNBOH-2-CI; Cimbi-27; 2C-I-NBOH; N-(2-Hydroxybenzyl)-4-iodo-2,5-dimethoxyphenethylamine
Routes of
administration 		Sublingual, buccal [1]
Drug class Serotonin 5-HT2 receptor agonist; Serotonergic psychedelic; Hallucinogen
Legal status
Legal status
Identifiers
  • 2-((2-(4-Iodo-2,5-dimethoxyphenyl)ethylamino)methyl)phenol
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C17H20INO3
Molar mass 413.255 g·mol−1
3D model (JSmol)
  • Oc2ccccc2CNCCc(c(OC)cc1I)cc1OC
  • InChI=1S/C17H20INO3/c1-21-16-10-14(18)17(22-2)9-12(16)7-8-19-11-13-5-3-4-6-15(13)20/h3-6,9-10,19-20H,7-8,11H2,1-2H3 Yes check.svgY
  • Key:FEUZHYRXGQTBRO-UHFFFAOYSA-N Yes check.svgY
   (verify)

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 [3] [4] and has also been encountered as a novel designer drug. [4] [5]

Contents

Use and effects

The dose range of 25I-NBOH is 300 to 1,000 μg, with an estimated typical dose of 700 μg. [1] [5] The route of administration is sublingual or buccal. [1]

Interactions

Pharmacology

Pharmacodynamics

25I-NBOH activities
Target Affinity (Ki, nM)
5-HT1A 2,220–>10,000 (Ki)
37,000 (EC50 Tooltip half-maximal effective concentration)
74% (Emax Tooltip maximal efficacy)
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 Tooltip μ-Opioid receptor47 (Ki)
1,330–23,400 (EC50)
16–55% (Emax)
DOR Tooltip δ-Opioid receptorND
KOR Tooltip κ-Opioid receptor328
TAAR1 Tooltip Trace amine-associated receptor 1ND
SERT Tooltip Serotonin transporter1,155–1,220 (Ki)
1,720 (IC50 Tooltip half-maximal inhibitory concentration)
Inactive (EC50)
NET Tooltip Norepinephrine transporter4,060 (Ki)
629 (IC50)
Inactive (EC50)
DAT Tooltip Dopamine transporter8,500 (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: [6] [7] [8] [9] [10] [11] [12]
[13] [3] [14] [15] [16] [17]

25I-NBOH acts as a potent agonist of the 5-HT2A receptor, [18] [19] 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. [20]

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. [16] [12] However, in another study, it only had about 6-fold selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor. [14]

25I-NBOH produces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents. [1]

Chemistry

Analytical chemistry

25I-NBOH is a labile molecule which fragments into 2C-I when analyzed by routine gas chromatography (GC) methods. [21] A specific method for reliable identification of 25I-NBOH using GC/MS has been reported, allowing forensic forces worldwide to correctly identify this compound. [22]

Analogues and derivatives

History

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

Society and culture

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]

See also

References

  1. 1 2 3 4 Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species" (PDF). Neuropharmacology. 167 107933. doi:10.1016/j.neuropharm.2019.107933. PMC   9191653 . PMID   31917152.
  2. ↑ Anvisa (2023-07-24). "RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-07-25). Archived from the original on 2023-08-27. Retrieved 2023-08-27.
  3. 1 2 Halberstadt AL (2017). "Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens". Current Topics in Behavioral Neurosciences. 32: 283–311. doi:10.1007/7854_2016_64. ISBN   978-3-319-52442-9. PMID   28097528.
  4. 1 2 Herian M, Świt P (January 2023). "25X-NBOMe compounds - chemistry, pharmacology and toxicology. A comprehensive review". Critical Reviews in Toxicology. 53 (1): 15–33. doi:10.1080/10408444.2023.2194907. PMID   37115704.
  5. 1 2 Arantes LC, Júnior EF, de Souza LF, Cardoso AC, Alcântara TL, Lião LM, et al. (2017). "25I-NBOH: a new potent serotonin 5-HT2A receptor agonist identified in blotter paper seizures in Brazil". Forensic Toxicology. 35 (2): 408–414. doi:10.1007/s11419-017-0357-x. PMC   5486617 . PMID   28706567.
  6. ↑ Braden MR, Parrish JC, Naylor JC, Nichols DE (December 2006). "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. doi:10.1124/mol.106.028720. PMID   17000863.
  7. ↑ Braden MR (2007). Towards a biophysical understanding of hallucinogen action (Ph.D. thesis). Purdue University. ProQuest   304838368.
  8. ↑ 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
  9. ↑ 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.
  10. ↑ 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". European Journal of Nuclear Medicine and Molecular Imaging. 38 (4): 681–693. doi:10.1007/s00259-010-1686-8. PMID   21174090.
  11. ↑ Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT 2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi: 10.1002/wmts.42 . ISSN   2190-460X.
  12. 1 2 Hansen M, Phonekeo K, Paine JS, Leth-Petersen S, Begtrup M, Bräuner-Osborne H, et al. (19 March 2014). "Synthesis and Structure–Activity Relationships of N -Benzyl Phenethylamines as 5-HT 2A/2C Agonists". ACS Chemical Neuroscience. 5 (3): 243–249. doi: 10.1021/cn400216u . ISSN   1948-7193. PMC   3963123 . PMID   24397362.
  13. ↑ Nichols DE (2018). "Chemistry and Structure-Activity Relationships of Psychedelics". Current Topics in Behavioral Neurosciences. 36: 1–43. doi:10.1007/7854_2017_475. ISBN   978-3-662-55878-2. PMID   28401524.
  14. 1 2 Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A (December 2018). "Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors". Biochemical Pharmacology. 158: 27–34. doi:10.1016/j.bcp.2018.09.024. PMC   6298744 . PMID   30261175.
  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". Archives of Toxicology. 94 (10): 3449–3460. Bibcode:2020ArTox..94.3449P. doi:10.1007/s00204-020-02836-w. PMID   32627074.
  16. 1 2 Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews. 124 (1): 124–163. 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
  17. ↑ Deventer MH, Persson M, Laus A, Pottie E, Cannaert A, Tocco G, et al. (May 2023). "Off-target activity of NBOMes and NBOMe analogs at the µ opioid receptor". Archives of Toxicology. 97 (5): 1367–1384. Bibcode:2023ArTox..97.1367D. doi:10.1007/s00204-023-03465-9. hdl:11584/434705. PMID   36853332.
  18. ↑ 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". European Journal of Nuclear Medicine and Molecular Imaging. 38 (4): 681–693. doi:10.1007/s00259-010-1686-8. PMID   21174090. S2CID   12467684.
  19. ↑ Silva ME, Heim R, Strasser A, Elz S, Dove S (January 2011). "Theoretical studies on the interaction of partial agonists with the 5-HT2A receptor". Journal of Computer-aided Molecular Design. 25 (1): 51–66. Bibcode:2011JCAMD..25...51S. CiteSeerX   10.1.1.688.2670 . doi:10.1007/s10822-010-9400-2. PMID   21088982. S2CID   3103050.
  20. ↑ Braden MR, Parrish JC, Naylor JC, Nichols DE (December 2006). "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. doi:10.1124/mol.106.028720. PMID   17000863. S2CID   15840304.
  21. ↑ Arantes LC, Júnior EF, de Souza LF, Cardoso AC, Alcântara TL, Lião LM, et al. (2017). "2A receptor agonist identified in blotter paper seizures in Brazil". Forensic Toxicology. 35 (2): 408–414. doi:10.1007/s11419-017-0357-x. PMC   5486617 . PMID   28706567.
  22. ↑ Neto JC, Andrade AF, Lordeiro RA, Machado Y, Elie M, Júnior EF, et al. (2017). "Preventing misidentification of 25I-NBOH as 2C-I on routine GC–MS analyses" (PDF). Forensic Toxicology. 35 (2): 415–420. doi:10.1007/s11419-017-0362-0. S2CID   32432586.
  23. ↑ Heim R, Elz S (March 2000). "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). ISSN   0365-6233. Archived from the original on 20 March 2025.
  24. ↑ Pertz HH, Heim R, Elz S (2000). "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). Archived from the original on 20 March 2025.
  25. ↑ Heim R (25 March 2003). "Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts" [Synthesis and pharmacology of potent 5-HT2A receptor agonists with an N-2-methoxybenzyl partial structure. Development of a new structure-activity concept.] (in German). diss.fu-berlin.de. Archived from the original on 2012-04-16. Retrieved 2013-05-10.
  26. ↑ "Gemensamma författningssamlingen avseende hälso- och sjukvård, socialtjänst, läkeme del, folkhälsa m.m." (PDF). Lakemedelsverket. Archived from the original (PDF) on 2017-10-30. Retrieved 2017-04-21.
  27. ↑ "The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014". UK Statutory Instruments 2014 No. 1106. www.legislation.gov.uk.


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