DOI-NBOMe
Pharmaceutical compound
From Wikipedia, the free encyclopedia
DOI-NBOMe, or NBOMe-DOI, also known as N-(2-methoxybenzyl)-4-iodo-2,5-dimethoxyamphetamine, is a non-hallucinogenic serotonin 5-HT2A receptor biased agonist of the phenethylamine, DOx, and 25-NB (NBOMe) families.[1][2][3][4][5] It is the N-(2-methoxybenzyl) derivative of DOI and the amphetamine (i.e., α-methyl) analogue of 25I-NBOMe.[4][3][5]
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| Other names | NBOMe-DOI; N-(2-Methoxybenzyl)-4-iodo-2,5-dimethoxyamphetamine; 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)amphetamine |
| Drug class | Non-hallucinogenic serotonin 5-HT2A receptor agonist |
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| Formula | C19H24INO3 |
| Molar mass | 441.309 g·mol−1 |
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Pharmacology
Pharmacodynamics
DOI-NBOMe is a potent serotonin 5-HT2A receptor partial agonist, with an affinity (Ki) of 0.78 to 1.08 nM, an EC50 of 36.1 nM, and an Emax of 43% in the employed assay.[4][3] As an agonist of the serotonin 5-HT2A 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 Ki of 0.58–0.64 nM, an EC50 of 19.2 nM, and an Emax of 77%).[4][3] Compared to 25I-NBOMe, the corresponding NBOMe analogue of 2C-I, DOI-NBOMe had about 14.4-fold lower potency as a serotonin 5-HT2A receptor agonist and slightly more than half the activational efficacy.[4][3] 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.[2][4][3][5][6][7]
Besides the serotonin 5-HT2A receptor, DOI-NBOMe has also been shown to bind to the serotonin 5-HT2C receptor, with an affinity (Ki) of 21.0 nM.[3] This was about 33-fold lower than the affinity of DOI.[3] As such, DOI-NBOMe appears to show increased selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor compared to DOI.[3] For comparison, 25I-NBOMe had increased affinities for both the serotonin 5-HT2A receptor and to a lesser extent the serotonin 5-HT2C receptor compared to 2C-I.[3]
Subsequent to its earlier discovery and characterization, DOI-NBOMe was found to be a biased agonist of the serotonin 5-HT2A receptor, with robust Gq activation comparable to DOI but minor efficacy on Gi signaling.[8] In addition, it was selective for the serotonin 5-HT2A receptor, with much less or no agonism of the 5-HT1A, 5-HT2B, or 5-HT2C receptors.[8] The EC50 (Emax) values were 10 nM (103%) at the serotonin 5-HT2A receptor (Gq) and 603 nM (145%) at the serotonin 5-HT2C receptor.[8] Values for Gq, Gi, and β-arrestin2 signaling at the serotonin 5-HT2A receptor were also reported.[8] DOI-NBOMe failed to produce the head-twitch response in rodents.[8] Moreover, DOI-NBOMe antagonized the head-twitch response induced by DOI or LSD.[8] The drug was found to produce rapid and sustained antidepressant-like effects in the forced swim test (FST) in rodents.[8] In addition, it produced sustained anxiolytic-like effects in the marble-burying test.[8] It was concluded that serotonin 5-HT2A receptor Gi signaling and not Gq signaling is involved in the psychedelic-like effects of serotonergic psychedelics.[8]
Chemistry
History
DOI-NBOMe was first described in the scientific literature by Ralf Heim by 2003.[5] However, Heim only synthesized DOI-NBOMe without reporting its pharmacology.[5] The pharmacological interactions of DOI-NBOMe were subsequently reported by Michael Braden and colleagues, from the lab of David E. Nichols, by 2006.[4][3] DOI-NBOMe was later further characterized in 2026.[8]