DOM-NBOMe

DOM-NBOMe, or NBOMe-DOM, also known as N-(2-methoxybenzyl)-4-methyl-2,5-dimethoxyamphetamine, is a serotonin 5-HT₂ receptor agonist and putative psychedelic drug of the phenethylamine, DOx, and 25-NB (NBOMe) families. It is the N-(2-methoxybenzyl) derivative of DOM and the amphetamine (i.e., α-methyl) analogue of 25D-NBOMe.

DOM-NBOMe is a potent agonist of the serotonin 5-HT₂ receptors, including the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors. Its affinity (K_i) for the serotonin 5-HT_2A receptor was reported to be 45.8 nM. In terms of functional activity, DOM-NBOMe showed an EC₅₀Tooltip half-maximal effective concentration of 4.25 nM and E_maxTooltip maximal efficacy of 88.8% at the serotonin 5-HT_2A receptor, an EC₅₀ of 54.6 nM and E_max of 20.1% at the serotonin 5-HT_2B receptor, and an EC₅₀ of 9.96 nM and E_max of 87.6% at the serotonin 5-HT_2C receptor. It was inactive as an agonist of the serotonin 5-HT_1A receptor, with an EC₅₀ of >10,000 nM. DOM-NBOMe showed 17-fold lower potency as a serotonin 5-HT_2A receptor agonist compared to 25D-NBOMe in vitro, while DOM was not assessed in the same study and thus DOM-NBOMe could not be compared to that compound. 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.

DOM-NBOMe has been assessed and found to produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. However, DOM-NBOMe showed a weak maximal head-twitch response compared to DOI. Whereas DOI induced a maximum of 36 head twitches in a 20-minute period, DOM-NBOMe produced a maximum of 12 head twitches in the same amount of time (i.e., about 33% of that of DOI). Hence, although DOM-NBOMe could still be an active psychedelic in humans, it may have attenuated hallucinogenic effects compared to non-25-NB DOx psychedelics. The doses of DOM-NBOMe producing the head-twitch response were not reported.

The in-vitro metabolism and cytochrome P450 (CYP450) inhibition of DOM-NBOMe have been studied.

DOM-NBOMe was first disclosed in a patent application (compound #17, example #16 in WO2022/192781) by Andrew Kruegel at Gilgamesh Pharmaceuticals by 2022.