DOI-NBOMe

DOI-NBOMe, or NBOMe-DOI, also known as N-(2-methoxybenzyl)-4-iodo-2,5-dimethoxyamphetamine, is a non-hallucinogenic serotonin 5-HT_2A receptor biased agonist of the phenethylamine, DOx, and 25-NB (NBOMe) families. It is the N-(2-methoxybenzyl) derivative of DOI and the amphetamine (i.e., α-methyl) analogue of 25I-NBOMe.

Pharmacology

Pharmacodynamics

DOI-NBOMe is a potent serotonin 5-HT_2A receptor partial agonist, with an affinity (K_i) of 0.78 to 1.08nM, an of 36.1nM, and an 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 0.58–0.64nM, an of 19.2nM, and an 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.

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 21.0nM. 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.

Subsequent to its earlier discovery and characterization, DOI-NBOMe was found to be a biased agonist of the serotonin 5-HT_2A receptor, with robust G_q activation comparable to DOI but minor efficacy on G_i signaling. In addition, it was selective for the serotonin 5-HT_2A receptor, with much less or no agonism of the 5-HT_1A, 5-HT_2B, or 5-HT_2C receptors. The () values were 10nM (103%) at the serotonin 5-HT_2A receptor (G_q) and 603nM (145%) at the serotonin 5-HT_2C receptor. Values for G_q, G_i, and β-arrestin2 signaling at the serotonin 5-HT_2A receptor were also reported. DOI-NBOMe failed to produce the head-twitch response in rodents. Moreover, DOI-NBOMe antagonized the head-twitch response induced by DOI or LSD. The drug was found to produce rapid and sustained antidepressant-like effects in the forced swim test (FST) in rodents. In addition, it produced sustained anxiolytic-like effects in the marble-burying test. It was concluded that serotonin 5-HT_2A receptor G_i signaling and not G_q signaling is involved in the psychedelic-like effects of serotonergic psychedelics.

Chemistry

Synthesis

The chemical synthesis of DOI-NBOMe has been described.

Analogues

Analogues of DOI-NBOMe include DOI, DOB-NBOMe, DOM-NBOMe, and 25I-NBOMe, among others.

History

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. DOI-NBOMe was later further characterized in 2026.

See also

• 25-NB
• DOx

References

External links

• DOI-NBOMe - Isomer Design