25B-NBOMe, also known asNBOMe-2C-B andCimbi-36, is apsychedelic drug of the25-NB (NBOMe) family derived from2C-B. It acts as a potentfull agonist for the5HT2Areceptor.[3][4][5] Duration of effects lasts about 3 to 10hours,[6] although the parent compound is rapidly cleared from the blood when used in the radiolabeled form in tracer doses.[7] Recently, Custodio et al. (2019) evaluated the potential involvement of dysregulated dopaminergic system, neuroadaptation, and brain wave changes which may contribute to the rewarding and reinforcing properties of 25B-NBOMe in rodents.[8]
The carbon-11 labeled version of this compound ([11C]Cimbi-36) was synthesized and validated as aradioactive tracer for positron emission tomography (PET) in Copenhagen.[9][10][11] As a 5-HT2A receptor agonist PET radioligand, [11C]Cimbi-36 was hypothesized to provide a more functional marker of these receptors. Also, [11C]Cimbi-36 is investigated as a potential marker of serotonin release and thus could serve as an indicator of serotonin levelsin vivo. [11C]Cimbi-36 is now undergoing clinical trials as a PET-ligand in humans.[12][13][14]
NBOMe and NBOHs are regularly sold as LSD in blotter papers,[18][26] which have a bitter taste and different safety profiles.[20][17] Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity.[17] Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,[22] and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".[20] 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.[27][28][20]
Given limited documentation of NBOMe consumption, the long-term effects of the substance remain unknown.[20] NBOMe compounds are not active orally,[a] and are usually taken sublingually.[30]: 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.[31][32][33]
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.[18][23] 5-HT2B receptors have been strongly implicated in causing drug-inducedvalvular heart disease.[34][35][36] The high affinity of NBOMe compounds foradrenergic α1 receptor has been reported to contribute to the stimulant-type cardiovascular effects.[23]
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.[19] 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.[19]
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.[37][38]
25B-NBOMe has been found to increase levels ofglutamate,serotonin,dopamine, andacetylcholine in thefrontal cortex,striatum, andnucleus accumbens in rats.[55] Other serotonergic psychedelics likeLSD andDOI have also been found to increase glutamate levels in the frontal cortex in rodents, and this effect can be blocked by the serotonin 5-HT2A receptor antagonistvolinanserin (MDL-100,907).[55] 25B-NBOMe shows aninverted U-shapeddose–response curve in terms ofneurotransmitter elevations in multiple brain areas.[55] This may be due to an inhibitory effect of serotonin 5-HT2C receptors at higher doses.[55] 25B-NBOMe produces thehead-twitch response, a behavioral proxy of psychedelic effects, in rodents, and this effect shows an inverted U-shaped dose–response curve similarly to its influences on neurotransmitter levels.[55] The head twitches and hallucinogenic effects of 25B-NBOMe may be due to increased cortical glutamate release secondary to serotonin 5-HT2A receptor activation.[55] The effects of 25B-NBOMe on levels of other neurotransmitters, such as accumbal dopamine concentrations, may also be mediated by activation of serotonin 5-HT2A receptors and glutamate elevation.[55] It has been suggested that the serotonin elevations with 25B-NBOMe may be involved in its production ofserotonin syndrome in humans.[54]
In Sweden, theRiksdag added 25B-NBOMe to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of August 1, 2013, published by theMedical Products Agency in their regulation LVFS 2013:15 listed as25B-NBOMe 2-(4-bromo-2,5-dimetoxifenyl)-N-(2-metoxibensyl)etanamin.[69]
In November 2013, the U.S. Drug Enforcement Administration placed 25B-NBOMe (along with25I-NBOMe and25C-NBOMe) in Schedule I of theControlled Substances Act, making it illegal to manufacture, buy, possess, process, or distribute.[71]
^Thepotency ofN-benzylphenethylamines via buccal, sublingual, or nasal absorption is 50- to 100-fold greater (by weight) than oral route compared to the parent2C-x compounds.[29] Researchers hypothesize the low oral metabolic stability ofN-benzylphenethylamines is likely causing the low bioavailability on the oral route, although the metabolic profile of this compounds remains unpredictable; therefore researchers state that the fatalities linked to these substances may partly be explained by differences in the metabolism between individuals.[29]
^Custodio RJ, Sayson LV, Botanas CJ, Abiero A, You KY, Kim M, et al. (November 2020). "25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential".Addiction Biology.25 (6) e12850.doi:10.1111/adb.12850.PMID31749223.S2CID208217863.
^Hansen M (December 16, 2010).Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain (Ph.D. thesis). University of Copenhagen.doi:10.13140/RG.2.2.33671.14245.
^abEttrup A, Hansen M, Santini MA, Paine J, Gillings N, Palner M, Lehel S, Herth MM, Madsen J, Kristensen J, Begtrup M, Knudsen GM (April 2011). "Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers".Eur J Nucl Med Mol Imaging.38 (4):681–693.doi:10.1007/s00259-010-1686-8.PMID21174090.
^Ettrup A, Holm S, Hansen M, Wasim M, Santini MA, Palner M, et al. (August 2013). "Preclinical safety assessment of the 5-HT2A receptor agonist PET radioligand [ 11C]Cimbi-36".Molecular Imaging and Biology.15 (4):376–383.doi:10.1007/s11307-012-0609-4.PMID23306971.S2CID1474367.
^abcdeJolanta Z, Monika K, and Piotr A (February 26, 2020)."NBOMes–Highly Potent and Toxic Alternatives of LSD".Frontiers in Neuroscience.14 78.doi:10.3389/fnins.2020.00078.PMC7054380.PMID32174803.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.
^Hansen, M. (2010). Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain: PhD Thesis. Faculty of Pharmaceutical Sciences, University of Copenhagen.https://bitnest.netfirms.com/external/Theses/Hansen2011
^Herth MM, Petersen IN, Hansen HD, Hansen M, Ettrup A, Jensen AA, Lehel S, Dyssegaard A, Gillings N, Knudsen GM, Kristensen JL (August 2016). "Synthesis and evaluation of (18)F-labeled 5-HT2A receptor agonists as PET ligands".Nucl Med Biol.43 (8):455–462.doi:10.1016/j.nucmedbio.2016.02.011.PMID27209485.
^Leth-Petersen S, Petersen IN, Jensen AA, Bundgaard C, Bæk M, Kehler J, Kristensen JL (November 2016). "5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism".ACS Chem Neurosci.7 (11):1614–1619.doi:10.1021/acschemneuro.6b00265.PMID27564969.
^Jensen AA, McCorvy JD, Leth-Petersen S, Bundgaard C, Liebscher G, Kenakin TP, Bräuner-Osborne H, Kehler J, Kristensen JL (June 2017). "Detailed Characterization of the In Vitro Pharmacological and Pharmacokinetic Properties of N-(2-Hydroxybenzyl)-2,5-Dimethoxy-4-Cyanophenylethylamine (25CN-NBOH), a Highly Selective and Brain-Penetrant 5-HT2A Receptor Agonist".J Pharmacol Exp Ther.361 (3):441–453.doi:10.1124/jpet.117.239905.PMID28360333.
^Åstrand A, Guerrieri D, Vikingsson S, Kronstrand R, Green H (December 2020). "In vitro characterization of new psychoactive substances at the μ-opioid, CB1, 5HT1A, and 5-HT2A receptors-On-target receptor potency and efficacy, and off-target effects".Forensic Sci Int.317 110553.doi:10.1016/j.forsciint.2020.110553.PMID33160102.
^Pottie E, Cannaert A, Stove CP (October 2020). "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor".Arch Toxicol.94 (10):3449–3460.Bibcode:2020ArTox..94.3449P.doi:10.1007/s00204-020-02836-w.PMID32627074.
^Zwartsen A, Verboven AH, van Kleef RG, Wijnolts FM, Westerink RH, Hondebrink L (December 2017). "Measuring inhibition of monoamine reuptake transporters by new psychoactive substances (NPS) in real-time using a high-throughput, fluorescence-based assay".Toxicol in Vitro.45 (Pt 1):60–71.Bibcode:2017ToxVi..45...60Z.doi:10.1016/j.tiv.2017.05.010.PMID28506818.
^abcdeWojtas A, Gołembiowska K (December 2023)."Molecular and Medical Aspects of Psychedelics".Int J Mol Sci.25 (1): 241.doi:10.3390/ijms25010241.PMC10778977.PMID38203411.Like 25I-NBOMe [55], 25B-NBOMe significantly increased the extracellular 5-HT levels [37]. This phenomenon may be the reason for the serotonin syndrome reported in humans after ingestion of 25B-NBOMe [51]. Furthermore, it increased the volume of dopaminergic neurotransmission akin to 25I-NBOMe. Those changes observed in NAC and STR suggest that it might exhibit reinforcing properties [37].
^abcdeCustodio RJ, Sayson LV, Botanas CJ, Abiero A, You KY, Kim M, Lee HJ, Yoo SY, Lee KW, Lee YS, Seo JW, Ryu IS, Kim HJ, Cheong JH (November 2020). "25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential".Addict Biol.25 (6) e12850.doi:10.1111/adb.12850.PMID31749223.
^Seo JY, Hur KH, Ko YH, Kim K, Lee BR, Kim YJ, Kim SK, Kim SE, Lee YS, Kim HC, Lee SY, Jang CG (October 2019). "A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents".Brain Res Bull.152:19–26.doi:10.1016/j.brainresbull.2019.07.002.PMID31279579.
^"关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. September 27, 2015. Archived fromthe original on October 1, 2015. RetrievedOctober 1, 2015.
Notes: (1) TAAR1 activity of ligands varies significantly between species. Some agents that are TAAR1 ligands in some species are not in other species. This navbox includes all TAAR1 ligands regardless of species. (2) See the individual pages for references, as well as theList of trace amines,TAAR, andTAAR1 pages. See also:Receptor/signaling modulators
