DOM-NBOMe, or NBOMe-DOM, also known as ''N''-(2-methoxybenzyl)-4-methyl-2,5-dimethoxyamphetamine, is a

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT₂ receptor

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

and putative

psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluc ...

of the

phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...

, DOx, and

25-NB The 25-NB (25''x''-NB''x'') series, or NBOMe series, also known as the ''N''-benzylphenethylamines, is a family of serotonergic psychedelics. They are substituted phenethylamines and were derived from the 2C family. The most commonly encountere ...

(NBOMe) families. Table 1. 5-HT2A receptor binding affinities of disclosed compounds. Table 3. Functional activity at 5-HT receptor subtypes. ..Table 4. Activity in the HTR assay in mice. .. It is the ''N''-(2-methoxybenzyl)

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

of DOM and the

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

(i.e., α-methyl) analogue of

25D-NBOMe 25D-NBOMe, also known as NBOMe-2C-D and "divination", is a derivative of the phenethylamine derived hallucinogen 2C-D. It acts in a similar manner to related compounds such as 25I-NBOMe, which is a potent agonist at the 5-HT2A receptor. 25D-NBOM ...

Pharmacology

Pharmacodynamics

DOM-NBOMe is a potent

of the serotonin 5-HT₂ receptors, including the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors. Its

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

(K_i) for the serotonin 5-HT_2A receptor was reported to be 45.8nM. In terms of

functional activity An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agoni ...

, DOM-NBOMe showed an of 4.25nM and of 88.8% at the serotonin 5-HT_2A receptor, an of 54.6nM and of 20.1% at the serotonin 5-HT_2B receptor, and an of 9.96nM and 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 of >10,000nM. DOM-NBOMe showed 17-fold lower potency as a serotonin 5-HT_2A receptor agonist compared to 25D-NBOMe ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'', 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 Substitution may refer to: Arts and media *Substitution (poetry), a variation in poetic scansion * Substitution (theatre), an acting methodology Music *Chord substitution, swapping one chord for a related one within a chord progression *Tritone ...

, 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 The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lys ...

, 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.

Pharmacokinetics

The ''in-vitro''

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

and

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

(CYP450)

inhibition Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransm ...

of DOM-NBOMe have been studied.

History

DOM-NBOMe was first disclosed in a

patent application A patent application is a request pending at a patent office for the grant of a patent for an invention described in the patent specification and a set of one or more claim (patent), claims stated in a formal document, including necessary officia ...

(compound #17, example #16 in WO2022/192781) by Andrew Kruegel at

Gilgamesh Pharmaceuticals Gilgamesh Pharmaceuticals is a pharmaceutical company that is developing psychedelic and related drugs as medicines. It is a "discovery stage" company and is focused on developing new chemical entities. Its drug candidates include the ketamine- ...

by 2022.

References

External links