DOI-NBOMe

The drug is a potent serotonin 5-HT_2A receptor partial agonist, with an affinity (K_i) of 0.78 to 1.08{{nbsp}}nM, an {{Abbrlink|EC₅₀|half-maximal effective concentration}} of 36.1{{nbsp}}nM, and an {{Abbrlink|E_max|half-maximal effective concentration}} of 43% in the employed assay. As an agonist of the serotonin 5-HT_2A receptor, DOI-NBOMe had about half the affinity and potency of DOI and a little more than half the efficacy in comparison in vitro (with DOI having a K_i of 0.58–0.64{{nbsp}}nM, an {{Abbr|EC₅₀|half-maximal effective concentration}} of 19.2{{nbsp}}nM, and an {{Abbr|E_max|half-maximal effective concentration}} of 77%). Compared to 25I-NBOMe, the corresponding NBOMe analogue of 2C-I, DOI-NBOMe had about 14.4-fold lower potency as a serotonin 5-HT_2A receptor agonist and slightly more than half the activational efficacy. Whereas the potency of 2Cs can be dramatically increased by N-(2-methoxybenzyl) substitution, this has not been the case with the DOx series of psychedelics, where activity has been negatively impacted.{{Cite thesis | vauthors = Silva M | title = Theoretical study of the interaction of agonists with the 5-HT2A receptor | year = 2009 | type = PhD. | url = http://epub.uni-regensburg.de/12119/ | publisher = Universität Regensburg | quote = Table 5.1: Agonistic potency (pEC50) and intrinsic activity (Emax) of 5-HT2AR partial agonistic arylethylamines (indole, methoxybenzene and quinazolinedione derivatives) used in the study. [...] [Compound] 234 [...] }}{{cite journal | vauthors = Silva ME, Heim R, Strasser A, Elz S, Dove S | title = Theoretical studies on the interaction of partial agonists with the 5-HT2A receptor | journal = Journal of Computer-aided Molecular Design | volume = 25 | issue = 1 | pages = 51–66 | date = January 2011 | pmid = 21088982 | doi = 10.1007/s10822-010-9400-2 | quote = Table 1 Structure, agonistic potency (pEC50) and efficacy (Emax) of r5-HT2AR partial agonistic arylethylamines [...] [Compound] 25 [...] On average, methyl groups in a-position of the ethyl side chain decrease activity. However, the effect of a-Me depends on the nature of the amino group: if one considers the pEC50 values and residuals (see Table 1), it becomes obvious that the methyl branch is favourable in primary amines (cpds. 11 and 12) and unfavourable in secondary benzylamines (cpds. 17 and 25). This different behavior may be simply due to a potential interaction of the a-Me group with the receptor which is not possible in the case of a bulky RN moiety because of restricted degrees of freedom for fit. A methyl group as part of a tertiary amine strongly lowers activity. }}

Besides the serotonin 5-HT_2A receptor, DOI-NBOMe has also been shown to bind to the serotonin 5-HT_2C receptor, with an affinity (K_i) of 21.0{{nbsp}}nM.{{cite thesis | vauthors = Braden MR | title = Towards a biophysical understanding of hallucinogen action | date = 2007 | degree = Ph.D. | publisher = Purdue University | id = {{ProQuest | 304838368}}|url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=9a30faca37ad48466b87a192ccd542401dc24012|quote=With the exceptions of the N-(2-methoxy)benzyl analogue of DOI (DOI-NBOMe), and the N-(2-napthyl)methyl analogue of 25I (25I-NNap) all N-arylmethyl analogues of phenylalkylamines followed this trend of increased binding affinity at the rat 5-HT2A receptor. [...] All compounds tested were relatively potent agonists at the cloned rat 5-HT2A receptor and possessed robust intrinsic activities, with the exception of DOI-NBOMe, 25I-NB 25I-NNap, and 25I-NBF, which were weak partial agonists. [...] Table 4.3 Effect of N-alkyl or N-aryl phenylalkylamine substitution on binding and functional activity at the rat 5-HT2A receptor. [...] Table A.1 Binding affinities at wild type human and rat 5-HT receptors. [...]}} This was about 33-fold lower than the affinity of DOI. As such, DOI-NBOMe appears to show increased selectivity for the serotonin 5-HT_2A receptor over the serotonin 5-HT_2C receptor compared to DOI. For comparison, 25I-NBOMe had increased affinities for both the serotonin 5-HT_2A receptor and to a lesser extent the serotonin 5-HT_2C receptor compared to 2C-I.

DOI-NBOMe was first described in the scientific literature by Ralf Heim by 2003. However, Heim only synthesized DOI-NBOMe without reporting its pharmacology. The pharmacological interactions of DOI-NBOMe were subsequently reported by Michael Braden and colleagues, from the lab of David E. Nichols, by 2006.

• DOB-NBOMe
• DOM-NBOMe
• 25-NB
• DOx

{{Reflist}}

• [https://isomerdesign.com/pihkal/explore/5387 DOI-NBOMe - Isomer Design]

{{Serotonin receptor modulators}}

{{Phenethylamines}}

Category:5-HT2A agonists

Category:25-NB (psychedelics)

Category:Iodobenzene derivatives

Category:DOx (psychedelics)

Category:2-Methoxyphenyl compounds

Category:Serotonin receptor modulators

{{Psychoactive-stub}}