5-DM-DOM

The properties and effects of 5-DM-DOM in humans have not been reported and are unknown.^[8]

5-DM-DOM shows affinity for the serotonin 5-HT_2A and 5-HT_2C receptors (K_i = 210 nM and 500 nM, respectively).^[1][9][3] Its affinity for the serotonin 5-HT_2A receptor was about 1.75-fold lower than that of DOM.^[9][3] In another earlier study, the drug's affinity (K_i) was 200 nM for the serotonin 5-HT₂ receptor, with this being about 2-fold lower than that of DOM.^[10] Conversely, in another later study, its affinity (K_0.5) was 4.8 nM for the serotonin 5-HT_2A receptor and was about the same as that of DOM (which was 4.4 nM).^[11] In addition, 5-DM-DOM was shown to be an agonist of the serotonin 5-HT_2A receptor, with an EC₅₀Tooltip half-maximal effective concentration (E_maxTooltip maximal efficacy) of 18.1 nM (101%), relative to 19.3 nM (95%) in the case of DOM.^[11]

5-DM-DOM fully generalized to (–)-DOM (the more active psychedelic enantiomer of DOM) and LSD in rodent drug discrimination tests.^[9][3] It produced 87.5% (–)-DOM-appropriate responding at a dose of 0.3 mg/kg and 94% LSD-appropriate responding at a dose of 3.0 mg/kg.^[3] For comparison, the training dose of (–)-DOM was 0.6 mg/kg.^[3] The drug's substitution was inhibited by the selective serotonin 5-HT_2A receptor antagonist volinanserin (MDL-100907).^[9][3] An earlier study on the other hand found that 5-DM-DOM across a dose range of 1.0 to 3.0 mg/kg failed to substitute for racemic DOM at a training dose of 1.0 mg/kg, with 5-DM-DOM at 1.0 to 2.0 mg/kg producing insignificant substitution (3–12%) and the 3.0 mg/kg dose producing behavioral disruption.^[5] The drug's ED₅₀Tooltip median effective dose could not be calculated nor compared with that of DOM or (–)-DOM in this study.^[5]

DOM shows an unusually delayed onset of effects in animals and humans compared to other psychedelics like LSD and mescaline.^[1][3][12] In rats, DOM produces peak interoceptive effects after 60 minutes, whereas LSD and mescaline do so after only 15 minutes.^[1][3] This cannot be explained by delayed uptake of DOM into the brain, as maximal brain levels of (–)-DOM in rats occur after 15 to 30 minutes.^[1][3] Based on these findings, it was theorized that DOM's delayed onset of effects might be due to formation of active metabolites such as 2-DM-DOM and 5-DM-DOM.^[1][3][13] As a result of their free hydroxyl group and consequent greater polarity, these metabolites are expected to cross the blood–brain barrier more slowly than DOM.^[1][9][5] The hypothesis was tested, but it could not be unequivocally accepted nor rejected.^[3] Both metabolites were said to be less potent than DOM itself.^[1][3][5][2] In any case, the metabolites showed a delayed time to peak interoceptive effects similarly to DOM in rats.^[1][9][3]

There have been concerns that 5-DM-DOM might be neurotoxic.^[9] This is because DOM has been found to undergo bis-demethylation into 2,5-DDM-DOM followed by subsequent oxidation to a reactive alkylating para-quinone and/or cyclic iminoquinone.^[9][14] The properties of the hydroquinone DOM metabolite have been said to parallel those of the monoaminergic neurotoxin 6-hydroxydopamine.^[14]

The predicted log P of 5-DM-DOM is 1.9^[15] and of DOM is 2.2.^[16]

5-DM-DOM was first described in the scientific literature as a DOM metabolite the mid-1970s.^{[3][6][17][7]} Subsequently, its pharmacology was described by Richard Glennon and colleagues in the early-to-mid 1980s^[5] and in the early 2000s.^[4][3]

• DOx (psychedelics)
• 2,5-DDM-DOM
• 2-OH-2C-B
• 5-DM-25B-NBOMe
• 3-O-Desmethylmescaline
• 4-O-Desmethylmescaline