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| Other names | 2C-N-NBOMe; NBOMe-2C-N |
| Drug class | Serotonin5-HT2A receptoragonist;Serotonergic psychedelic;Hallucinogen |
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| Chemical and physical data | |
| Formula | C18H22N2O5 |
| Molar mass | 346.383 g·mol−1 |
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25N-NBOMe, also known as2C-N-NBOMe orNBOMe-2C-N, is aderivative of thehallucinogen2C-N. The pharmacological properties of 25N-NBOMe have not been described in the scientific literature, but it is believed to act in a similar manner to related compounds such as25I-NBOMe and25C-NBOMe, which are potentagonists at the5HT2Areceptor.[2][3] 25N-NBOMe has been sold as a street drug and has only been described in the literature in terms of identification by forensic analysis.[4][5]
The dose range of 25N-NBOMe has been given as 0.1 to 1.3 mg or moresublingually, with a typical dose estimate of 0.6 mg.[6] Whereas2C-N is much lesspotent in terms of dose than other2C drugs, 25N-NBOMe appears to have a similar dose range as otherNBOMe drugs.[6]
NBOMe compounds are often associated with life-threatening toxicity and death.[7][8] Studies on NBOMe family of compounds demonstrated that the substance exhibit neurotoxic and cardiotoxic activity.[9] Reports ofautonomic dysfunction remains prevalent with NBOMe compounds, with most individuals experiencingsympathomimetic toxicity such asvasoconstriction,hypertension andtachycardia in addition to hallucinations.[10][11][12][13][14] Other symptoms oftoxidrome include agitation oraggression,seizure,hyperthermia,diaphoresis,hypertonia,rhabdomyolysis, and death.[10][14][8] Researchers report that NBOMe intoxication frequently display signs ofserotonin syndrome.[15] The likelihood of seizure is higher in NBOMes compared to other psychedelics.[9]
NBOMe and NBOHs are regularly sold as LSD in blotter papers,[8][16] which have a bitter taste and different safety profiles.[10][7] Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity.[7] Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,[12] and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".[10] While most fatalities are due to the physical effects of the drug, there have also been reports of death due toself-harm and suicide under the influence of the substance.[17][18][10]
Given limited documentation of NBOMe consumption, the long-term effects of the substance remain unknown.[10] NBOMe compounds are not active orally,[a] and are usually taken sublingually.[20]: 3 When NBOMes are administered sublingually,numbness of the tongue and mouth followed by a metallic chemical taste was observed, and researchers describe this physical side effect as one of the main discriminants between NBOMe compounds and LSD.[21][22][23]Many of the NBOMe compounds have high potency agonist activity at additional 5-HT receptors and prolonged activation of 5-HT2B can cause cardiac valvulopathy in high doses and chronic use.[8][13] 5-HT2B receptors have been strongly implicated in causing drug-inducedvalvular heart disease.[24][25][26] The high affinity of NBOMe compounds foradrenergic α1 receptor has been reported to contribute to the stimulant-type cardiovascular effects.[13]
In vitro studies, 25C-NBOMe has been shown to exhibitcytotoxicity on neuronal cell linesSH-SY5Y,PC12, and SN471, and the compound was more potent thanmethamphetamine at reducing the visibility of the respective cells; the neurotoxicity of the compound involves activation ofMAPK/ERK cascade and inhibition ofAkt/PKB signaling pathway.[9] 25C-NBOMe, including the other derivative25D-NBOMe, reduced the visibility ofcardiomyocytes H9c2 cells, and both substances downregulated expression level of p21 (CDC24/RAC)-activated kinase 1 (PAK1), an enzyme with documented cardiac protective effects.[9]
Preliminary studies on 25C-NBOMe have shown that the substance is toxic to development, heart health, and brain health inzebrafish, rats, andArtemia salina, a common organism for studying potential drug effects on humans, but more research is needed on the topic, the dosages, and if the toxicology results apply to humans. Researchers of the study also recommended further investigation of the drug's potential in damaging pregnant women and their fetus due to the substance's damaging effects to development.[27][28]| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 1,860–4,200 (Ki) 4,800 (EC50Tooltip half-maximal effective concentration) 36% (EmaxTooltip maximal efficacy) |
| 5-HT1B | >10,000 |
| 5-HT1D | 5,620 |
| 5-HT1E | >10,000 |
| 5-HT1F | ND |
| 5-HT2A | 0.11–1.41 (Ki) 0.204–70 (EC50) 34–137% (Emax) |
| 5-HT2B | 4.47–8.7 (Ki) 2.34–70 (EC50) <10–58% (Emax) |
| 5-HT2C | 1.06–21 (Ki) 0.457–1.32 (EC50) 99–102% (Emax) |
| 5-HT3 | >10,000 |
| 5-HT4 | ND |
| 5-HT5A | >10,000 |
| 5-HT6 | 55 |
| 5-HT7 | >10,000 |
| α1A | 850–>10,000 |
| α1B,α1D | >10,000 |
| α2A | 501–590 |
| α2B | 1,100 |
| α2C | 692 |
| β1 | >10,000 |
| β1 | 7,080 |
| β3 | >10,000 |
| D1 | 18,000 |
| D2 | 2,400–6,760 |
| D3 | 2,190–4,500 |
| D4 | >10,000 |
| D5 | >10,000 |
| H1 | 91–210 |
| H2 | 1,070 |
| H3,H4 | >10,000 |
| M1–M5 | >10,000 |
| I1 | ND |
| σ1 | 537 |
| σ2 | 58 |
| MOR | >10,000 |
| DOR | >10,000 |
| KOR | 2,820 |
| TAAR1Tooltip Trace amine-associated receptor 1 | >20,000 (Ki) (mouse) 2,200 (Ki) (rat) >30,000 (EC50) (mouse) 1,500 (EC50) (rat) >10,000 (EC50) (human) IA (Emax) (mouse) 34% (Emax) (rat) |
| SERTTooltip Serotonin transporter | 1,410–5,810 (Ki) 5,790–20,000 (IC50Tooltip half-maximal inhibitory concentration) IA (EC50) |
| NETTooltip Norepinephrine transporter | 7,200–11,300 (Ki) 15,000–33,000 (IC50) IA (EC50) |
| DATTooltip Dopamine transporter | 13,000–37,900 (Ki) 245,000 (IC50) IA (EC50) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified.Refs:[29][30][31][32][33][34][35] | |
25N-NBOMe is aselective and highlypotentagonist of theserotonin5-HT2 receptors.[36] Itsaffinities (Ki) are 0.144 nM at the serotonin5-HT2A receptor, 8.7 nM at the serotonin5-HT2B receptor, and 1.06 nM at the serotonin5-HT2C receptor.[36] In terms of affinity, the drug has approximately 7.4-fold selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor and 60-fold selectivity for the 5-HT2A receptor over the serotonin 5-HT2B receptor.[36]
TheEC50Tooltip half-maximal effective concentration (EmaxTooltip maximal efficacy) values of 25N-NBOMe are 0.51 nM (87.9%) at the serotonin 5-HT2A receptor, 47 nM (57.6%) at the serotonin 5-HT2B receptor, and 1.32 nM (99.4%) at the serotonin 5-HT2C receptor.[36] Hence, 25N-NBOMe is afull agonist of the serotonin 5-HT2A and 5-HT2C receptors and apartial agonist of the serotonin 5-HT2B receptor.[36] In terms offunctional activity, 25N-NBOMe had 2.6-fold selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor and 92-fold selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor.[36]
In a 2023 study, the pharmacological properties of 25N-NBOMe (also referred to as compound 4) were extensively characterized using bothin vitro andin vivo models.[37] Radioligand binding assays showed highbinding affinity forserotonin 5-HT2 receptors, with pKi values of 9.26 ± 0.15 at 5-HT2A, 8.35 ± 0.08 at 5-HT2B, and 8.16 ± 0.07 at 5-HT2C. The compound was also screened across more than 40 additional CNS targets and found to be highly selective for the 5-HT2 receptor subfamily.[37]
In calcium flux functional assays, 25N-NBOMe was a potent fullagonist at 5-HT2A (pEC50 = 9.50 ± 0.03; Emax = 94 ± 1%) and 5-HT2C (pEC50 = 9.07 ± 0.03; Emax = 102 ± 1%) receptors, while showing negligible agonist activity at 5-HT2B (Emax < 10%).[37]
Bioluminescence resonance energy transfer (BRET) functional assays measuring Gq dissociation andβ-arrestin2 recruitment signaling indicated strongagonist activity at 5-HT2A, with Gq pEC50 = 9.69 ± 0.04 (Emax = 95.2 ± 1.2%) and β-arrestin2 recruitment pEC50 = 9.66 ± 0.09 (Emax = 136.5 ± 3.6%). This illustrates that 25N-NBOMe is a balanced 5-HT2A agonist across these pathways, in contrast to analogs like25N-N1-Nap and25N-NBPh which displayedfunctional selectivity or signaling bias for β-arrestin2 recruitment. For 5-HT2C, Gq pEC50 was 9.34 ± 0.08 (Emax = 100.0 ± 2.5%), while weak partial agonist activity was observed at 5-HT2B (pEC50 = 8.63 ± 0.14; Emax = 54.1 ± 2.5%).[37]
In vivo, 25N-NBOMe induced a robusthead-twitch response (HTR) in mice with an ED50 of 0.11 mg/kg (0.29 μmol/kg). Notably 25N-NBOMe produced the highest HTR frequency (4.890 counts per minute) among a panel of structurally related 25N analogs.[37]
Unlike many otherserotonergic psychedelics, 25N-NBOMe has shownreinforcing effects in rodents, including in terms ofconditioned place preference (CPP) andself-administration.[38] 25N-NBOMe has been found to increasephosphorylation of thedopamine transporter (DAT) in thestriatum similarly tomethamphetamine in rodents.[39][38] DAT phosphorylation is associated withdopaminereverse transport andefflux, which in turn increasesextracellular dopamine levels.[39][38]
25N-NBOMe was first described in thescientific literature by 2012.[40]
25N-NBOMe is illegal in Hungary.[41]
The Riksdag added 25N-NBOMe toNarcotic Drugs Punishments Act underswedish schedule I ("substances, plant materials and fungi which normally do not have medical use") as of January 16, 2015, published byMedical Products Agency (MPA) in regulationLVFS 2014:11 listed as 25N-NBOMe, and 2-(2,5-dimetoxi-4-nitrofenyl)-N-(2-metoxibensyl)etanamin.[42]
This substance is aClass A drug in the United Kingdom as a result of theN-benzylphenethylamine catch-all clause in theMisuse of Drugs Act 1971.[43]
25N-NBOMe is illegal in Alabama.[44]
Supplementary Table S2. Dose estimates and data sources for psychedelics.
Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT2A and 5-HT2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT2A compared with 5-HT1A. They display higher affinity for 5-HT2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT2B receptor compared to 5-HT2A or 5-HT2C.
25N-NBOMe and other 2C drug derivatives similarly increased p-DAT levels in the NAc and striatum of mice (Seo et al. 2019). [...] increased p-DAT levels lead to an increase in dopamine release, which contribute to elevated dopamine levels.
