Pharmacokinetics, systemic toxicity, thermoregulation and acute behavioural effects of 25CN-NBOMe.

Autor: Šíchová K; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic., Syrová K; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic.; Third Faculty of Medicine, Charles University, Prague, Czech Republic., Kofroňová E; Forensic Laboratory of Biologically Active Compounds, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czech Republic., Pinterova-Leca N; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic., Vejmola Č; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic.; Third Faculty of Medicine, Charles University, Prague, Czech Republic., Nykodemová J; Forensic Laboratory of Biologically Active Compounds, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czech Republic., Palivec P; Forensic Laboratory of Biologically Active Compounds, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czech Republic., Olejníková L; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic., Danda H; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic.; Third Faculty of Medicine, Charles University, Prague, Czech Republic., Jorratt P; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic.; Third Faculty of Medicine, Charles University, Prague, Czech Republic., Adam Š; First Faculty of Medicine, Institute of Pathology, Charles University, Prague, Czech Republic., Hiep BQ; First Faculty of Medicine, Institute of Pathology, Charles University, Prague, Czech Republic., Štefková-Mazochová K; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic., Končická M; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic., Kuchař M; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic.; Forensic Laboratory of Biologically Active Compounds, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czech Republic., Páleníček T; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic.; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Jazyk: angličtina
Zdroj: Addiction biology [Addict Biol] 2022 Sep; Vol. 27 (5), pp. e13216.
DOI: 10.1111/adb.13216
Abstrakt: N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT 2A 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.
(© 2022 Society for the Study of Addiction.)
Databáze: MEDLINE
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