NBOMe
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N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT2A agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effect. Here, we investigated pharmacokinetics, systemic toxicity, thermoregulation in individually and group-housed animals, and acute behavioural effects after subcutaneous administration of 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe; 0.2, 1, and 5 mg/kg) in Wistar rats. Drug concentration peaked 1 h after the administration of 5 mg/kg in both blood serum and brain tissue with a half-life of 1.88 and 2.28 h, respectively. According to Organisation for Economic Co-operation and Development 423 toxicity assay, the drug is classified into category 3 with a lethal dose of 300 mg/kg and an estimated LD50 value of 200 mg/kg. Histological examination of organs collected from rats injected with the lethal dose revealed subtle pathological changes, highly suggestive of acute cardiovascular arrest due to malignant arrhythmia. Altered thermoregulation after 5 mg/kg was demonstrated by reduced body temperature in individually housed rats (p < 0.01). Behavioural effects assessed by the Open Field test and Prepulse Inhibition of Startle Response revealed that the two lower doses (0.2 and 1 mg/kg) caused a reduction in locomotor activity (p < 0.01), increased anxiety (p < 0.05) and 5 mg/kg additionally impaired sensorimotor gating (p < 0.001). In summary, 25CN-NBOMe readily passes the blood-brain barrier and exhibits a moderate level of toxicity and behavioural effect comparable with other NBOMes.
Introduction:N-2-methoxy-benzylated ("NBOMe") analogues of phenethylamine are a group of new psychoactive substances (NPS) with reported strong psychedelic effects in sub-milligram doses linked to a number of severe intoxications, including fatal ones. In our present work, we provide a detailed investigation of pharmacokinetics and acute behavioural effects of 2C-B-Fly-NBOMe (2-(8-bromo-2,3,6,7-tetrahydrobenzo [1,2-b:4,5-b']difuran-4-yl)-N-[(2-methoxybenzyl]ethan-1-amine), an analogue of popular psychedelic entactogen 2C-B (4-Bromo-2,5-dimethoxyphenethylamine). Methods: All experiments were conducted on adult male Wistar rats. Pharmacokinetic parameters of 2C-B-Fly-NBOMe (1 mg/kg subcutaneously; s. c.) in blood serum and brain tissue were analysed over 24 h using liquid chromatography-mass spectrometry (LC/MS). For examination of behavioural parameters in open field test (OFT) and prepulse inhibition (PPI) of acoustic startle reaction (ASR), 2C-B-Fly-NBOMe (0.2, 1 and 5 mg/kg s. c.) was administered in two temporal onsets: 15 and 60 min after administration. Thermoregulatory changes were evaluated in individually and group-housed animals over 8 h following the highest dose used in behavioural experiments (5 mg/kg s. c.). Results: Peak drug concentrations were detected 30 and 60 min after the drug application in serum (28 ng/ml) and brain tissue (171 ng/g), respectively. The parental compound was still present in the brain 8 h after administration. Locomotor activity was dose-dependently reduced by the drug in both temporal testing onsets. ASR was also strongly disrupted in both temporal onsets, drug's effect on PPI was weaker. 2C-B-Fly-NBOMe did not cause any significant thermoregulatory changes. Discussion: Our results suggest that 2C-B-Fly-NBOMe penetrates animal brain tissue in a relatively slow manner, induces significant inhibitory effects on motor performance, and attenuates sensorimotor gating. Its overall profile is similar to closely related analogue 2C-B and other NBOMe substances.
- Publikační typ
- časopisecké články MeSH
N-Benzylphenethylamines are novel psychedelic substances increasingly used for research, diagnostic, or recreational purposes. To date, only a few metabolism studies have been conducted for N-2-methoxybenzylated compounds (NBOMes). Thus, the available 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe) metabolism data are limited. Herein, we investigated the metabolic profile of 25CN-NBOMe in vivo in rats and in vitro in Cunninghamella elegans (C. elegans) mycelium and human liver microsomes. Phase I and phase II metabolites were first detected in an untargeted screening, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification of the most abundant metabolites by comparison with in-house synthesized reference materials. The major metabolic pathways described within this study (mono- and bis-O-demethylation, hydroxylation at different positions, and combinations thereof, followed by the glucuronidation, sulfation, and/or N-acetylation of primary metabolites) generally correspond to the results of previously reported metabolism of several other NBOMes. The cyano functional group was either hydrolyzed to the respective amide or carboxylic acid or remained untouched. Differences between species should be taken into account in studies of the metabolism of novel substances.
- Publikační typ
- časopisecké články MeSH
Compounds from the N-benzylphenethylamine (NBPEA) class of novel psychoactive substances are being increasingly utilized in neurobiological and clinical research, as diagnostic tools, or for recreational purposes. To understand the pharmacology, safety, or potential toxicity of these substances, elucidating their metabolic fate is therefore of the utmost interest. Several studies on NBPEA metabolism have emerged, but scarce information about substances with a tetrahydrobenzodifuran ("Fly") moiety is available. Here, we investigated the metabolism of 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)-N-(2-methoxybenzyl)ethan-1-amine (2C-B-Fly-NBOMe) in three different systems: isolated human liver microsomes, Cunninghamella elegans mycelium, and in rats in vivo. Phase I and II metabolites of 2C-B-Fly-NBOMe were first detected in an untargeted screening and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Several hypothesized metabolites were then synthesized as reference standards; knowledge of their fragmentation patterns was utilized for confirmation or tentative identification of isomers. Altogether, thirty-five phase I and nine phase II 2C-B-Fly-NBOMe metabolites were detected. Major detected metabolic pathways were mono- and poly-hydroxylation, O-demethylation, oxidative debromination, and to a lesser extent also N-demethoxybenzylation, followed by glucuronidation and/or N-acetylation. Differences were observed for the three used media. The highest number of metabolites and at highest concentration were found in human liver microsomes. In vivo metabolites detected from rat urine included two poly-hydroxylated metabolites found only in this media. Mycelium matrix contained several dehydrogenated, N-oxygenated, and dibrominated metabolites.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: New psychoactive substances (NPS) are on offer worldwide online, in order to shed light on the purity and price of these substances in the European Union, a research collaboration was set up involving France, United Kingdom (UK), the Netherlands, Czech Republic and Poland. METHODS: Per country, around 10 different NPS were test purchased from different webshops. Then, chemical analysis of NPS was done with according reference standards to identify and quantify the contents. RESULTS: In contrast to what is generally advertised on the webshops (>99%), purity varied considerably per test purchased NPS. Several NPS were mislabelled, some containing chemical analogues (e.g. 25B/C-NBOMe instead of 25I-NBOMe, pentedrone instead of 3,4-DMMC). But in some cases NPS differed substantially from what was advertised (e.g. pentedrone instead of AMT or 3-FMC instead of 5-MeO-DALT). Per gram, purity-adjusted prices of cathinones differed substantially between three countries of test purchase, with Poland being the least expensive. Synthetic cannabinoids were relatively the most expensive in the Czech Republic and least expensive in the UK. CONCLUSION: The current findings provides a snapshot of the price and chemical contents of NPS products purchased by different countries and in different webshops. There is a potential danger of mislabelling of NPS. The great variety in price and purity of the delivered products might be the result of the market dynamics of supply and demand and the role of law enforcement in different European countries.
- MeSH
- kontaminace léku * MeSH
- lidé MeSH
- obchod statistika a číselné údaje MeSH
- zakázané drogy chemie ekonomika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
... Nikotinové sáčky 129 -- 7.2 Kratom 131 -- 7.3 HHC 133 -- 7.4 HHC-P 135 -- 7.5 Fentanyl 136 -- 7.6 NBOMe ...
INTRODUCTION: Individuals who visit nightclubs and electronic dance music (EDM) festivals tend to use psychoactive substances, often multiple substances, in this setting and are at risk of serious negative health effects. This paper aims to explore respondents’ experiences and perceptions in order to have a better understanding of patterns and motives related to psychoactive substance use and high-risk behaviours in EDM event attendees. METHODS: In-depth and focus group interviews with 30 EDM event attendees who reported psychoactive substance use at nightlife events. The data was analysed using the Nvivo-v.10 software. RESULTS: Mixing multiple substances to get the desired effects was common. Ecstasy was often combined with Jager (alcohol). Drug use in nightlife settings occurred in a group of friends and was perceived as an essential part of having a good time. Most participants reported that they did not use drugs outside nightlife settings. The dangerous synthetic hallucinogen NBOMe was still on the scene. The respondents had a very low level of knowledge about, and perception of, the risks associated with drug consumption. Knowledge about risk minimisation strategies was very low or non-existent. CONCLUSIONS: Polydrug use and a lack of perceived harmful effects put drug-using nightlife attendees at increased risk of negative health consequences. Future research should focus on identifying strategies to raise the awareness of people who use drugs in nightlife settings and encourage them to employ health protection strategies. Using the social network infrastructure can be thought of as one potentially beneficial approach.
