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| Other names | 5-O-Desmethyl-DOM; 5-DES-Me-DOM; 5-OH-DOM; 5-Hydroxy-DOM; 5-HMMP; 5-Hydroxy-2-methoxy-4-methylamphetamine; 2-Methoxy-5-hydroxy-4-methylamphetamine |
| Drug class | Serotonin receptor modulator;Serotonin5-HT2 receptormodulator;Serotonergic psychedelic;Hallucinogen |
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| Formula | C11H17NO2 |
| Molar mass | 195.262 g·mol−1 |
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5-DM-DOM, also known as5-O-desmethyl-DOM,5-OH-DOM, or5-hydroxy-2-methoxy-4-methylamphetamine (5-HMMP), is apsychedelic drug of thephenethylamine andamphetamine families related to theDOx psychedelicDOM (2,5-dimethoxy-4-methylamphetamine; STP).[1][2][3][4][5] It has been identified as anactive metabolite of DOM in animals.[1][3][6][7] The drug is one of two possibleO-demethylatedanalogues and metabolites of DOM, the other being2-DM-DOM (2-O-desmethyl-DOM; 2-OH-DOM; 2-HMMP).[1][3][6]
The properties and effects of 5-DM-DOM in humans have not been reported and are unknown.[8]
5-DM-DOM showsaffinity for theserotonin5-HT2A and5-HT2C receptors (Ki = 210 nM and 500 nM, respectively).[1][9][3] Its affinity for the serotonin 5-HT2A receptor was about 1.75-fold lower than that of DOM.[9][3] In another earlier study, the drug's affinity (Ki) was 200 nM for the serotonin5-HT2 receptor, with this being about 2-fold lower than that of DOM.[10] Conversely, in another later study, its affinity (K0.5) was 4.8 nM for the serotonin 5-HT2A 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 anagonist of the serotonin 5-HT2A receptor, with anEC50Tooltip half-maximal effective concentration (EmaxTooltip 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 psychedelicenantiomer of DOM) andLSD in rodentdrug 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 theselective serotonin 5-HT2A receptorantagonistvolinanserin (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 forracemic 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'sED50Tooltip median effective dose could not be calculated nor compared with that of DOM or (–)-DOM in this study.[5]
DOM shows an unusually delayedonset of effects in animals and humans compared to other psychedelics like LSD andmescaline.[1][3][12] In rats, DOM produces peakinteroceptive 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 as2-DM-DOM and 5-DM-DOM.[1][3][13] As a result of their freehydroxyl group and consequent greaterpolarity, these metabolites are expected to cross theblood–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 lesspotent 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 beneurotoxic.[9] This is because DOM has been found to undergobis-demethylation into2,5-DDM-DOM followed by subsequentoxidation to areactivealkylatingpara-quinone and/or cyclic iminoquinone.[9][14] The properties of the hydroquinone DOM metabolite have been said to parallel those of themonoaminergic neurotoxin6-hydroxydopamine.[14]
The predictedlog P of 5-DM-DOM is 1.9[15] and of DOM is 2.2.[16]
5-DM-DOM was first described in thescientific literature as a DOM metabolite the mid-1970s.[3][6][17][7] Subsequently, itspharmacology was described byRichard Glennon and colleagues in the early-to-mid 1980s[5] and in the early 2000s.[4][3]
Examination of 2-HMMP, the 2-desmethyl metabolite of DOM (also called 2-DM DOM), and 5-HMMP, the 5-desmethyl metabolite (also called 5-DM DOM) (Figure 4-5), a positional isomer of 2-HMMP, showed that DOM-stimulus generalization occurred to 2-HMMP (ED50 = 1.71 mg/kg), but that administration of low doses of 5-HMMP produced only saline-like responding followed, at a higher dose, by disruption of the animals' behavior [7]. With a different training drug [i.e., (+)LSD], pre-session injection interval, and strain of rat (Fischer 344 rather than Sprague-Dawley), the (+)LSD stimulus generalized to both metabolites with the 5-desmethyl metabolite 5-HMMP being approximately twice as potent as its positional isomer [8]. [...] Figure 4-5. Chemical structures of the hallucinogen DOM, [...] its 2-desmethyl analog 2-HMMP (also known as 2-DM-DOM) and its positional isomer 5-HMMP (also known as 5-DM-DOM).
The metabolism of [DOM (111)] has been examined in some detail. [...] FIG. 9. Metabolic pathways for amine 111 (DOM). [...] The third general metabolic pathway for 111 is oxidative O-demethylation of the methyl phenyl ether groups. All three possible O-demethylated metabolites, compounds 118-120, have been characterized in rabbit liver homogenates (Zweig and Castagnoli, 1975, 1977). [...]
Another strategy was to unmask one of the two methoxy groups of DOB to provide a polar phenolic group – phenolic groups being known to decrease BBB permeability. We had already examined the two des-methyl analogs of DOM: 2-des-methyl DOM (2-DM-DOM; 26) and 5-des-methyl DOM (5-DM-DOM; 27) (Figure 8).43 Both compounds displayed affinity at 5-HT2A receptors, their affinities being approximately one-fifth and one-half, respectively, that of DOM. Furthermore, both compounds substituted in R(-)DOM-trained and LSD-trained animals, suggesting agonist action, and stimulus effects were antagonized by pretreatment of the animals with the selective phenylalkylamine-based 5-HT2A receptor antagonist M100907 (MDL-100,907; volinanserin, 28).43 Stimulus generalization was demonstrated to be time-dependent, with the phenolic compounds having a longer onset of action time (decreased ability of the agents to penetrate the BBB?). Both of these agents were potential candidates for further investigation. However, there was some concern that 2-DM-DOM and 5-DM-DOM might undergo further O-demethylation in vivo to a hydroquinone. It had been shown years earlier that DOM can undergo metabolic bis-demethylation to a hydroquinone, and that the hydroquinone undergoes oxidation to a para-quinone (and/or a cyclic iminoquinone) that reacts irreversibly with various proteins.44 As a consequence, this approach was not pursued because of potential risks of neurotoxicity.
{{cite thesis}}: CS1 maint: bot: original URL status unknown (link)The lengthy duration may additionally involve the formation of two active metabolites, 1-(2-hydroxy-5-methoxy4-methylphenyl)propan-2-amine and 1-(5-hydroxy-2-methoxy4-methylphenyl)propan-2-amine.35,36 These have been suggested to have greater effectiveness at behavioral disruption in rats than DOM.35 Their effects would be perceived of as a second intensity peak beginning when a user would typically anticipate a drug to be wearing off. This suggestion may be supported by the metabolism of DOM reported in rats by Zweig and Castagnoli36 and Eckler35 but is presently remains unproven for humans due to scant and inadequate studies of DOM's metabolism in humans. Shulgin also voiced suspicions of DOM producing an active metabolite in humans.4 Snyder observed that only between 5% and 10%34 or 5–20%14 of an administered dose of DOM was excreted unchanged, suggesting that significant levels of metabolism may occur in humans.