25I-NBOH acts as a potentagonist of the5-HT2A receptor,[18][19] with aKi of 0.061 nM at the human 5-HT2A receptor, similar to the better-known compound25I-NBOMe, making it some twelve times the potency of 2C-I itself.
Althoughin vitro tests show this compound acts as anagonist, animal studies to confirm these findings have not been reported. While theN-benzyl derivatives of 2C-I had significantly increased binding to5-HT2A receptor fragments, compared to 2C-I, theN-benzyl derivatives ofDOI, such asDOI-NBOMe, were less active compared to DOI.[20]
25I-NBOH is notable in having been found to be one of the mostselective agonists of the serotonin 5-HT2A receptor known, with an EC50 value of 0.074nM 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 is a labile molecule which fragments into 2C-I when analyzed by routinegas chromatography (GC) methods.[21] A specific method for reliable identification of 25I-NBOH usingGC/MS has been reported, allowing forensic forces worldwide to correctly identify this compound.[22]
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 byMedical Products Agency MPA) in regulationHSLF-FS 2015:12 listed as "25I-NBOH" and "2-([2-(4-jodo-2,5-dimetoxifenyl)etylamino]metyl)fenol".[26]
^abHerian 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.PMID37115704.
^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.PMID21174090.
^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.PMID32627074.
^abDuan 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.PMID38033123.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
^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.PMID21174090.S2CID12467684.
