Acute pharmacological profile of 2C-B-Fly-NBOMe in male Wistar rats-pharmacokinetics, effects on behaviour and thermoregulation.

Autor:	Syrová K; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.; Third Faculty of Medicine, Charles University, Prague, Czechia., Šíchová K; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia., Danda H; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.; Third Faculty of Medicine, Charles University, Prague, Czechia., Lhotková E; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia., Jorratt P; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.; Third Faculty of Medicine, Charles University, Prague, Czechia., Pinterová-Leca N; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.; Third Faculty of Medicine, Charles University, Prague, Czechia., Vejmola Č; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.; Third Faculty of Medicine, Charles University, Prague, Czechia., Olejníková-Ladislavová L; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.; Third Faculty of Medicine, Charles University, Prague, Czechia., Hájková K; Forensic Laboratory of Biologically Active Compounds, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czechia., Kuchař M; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.; Forensic Laboratory of Biologically Active Compounds, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czechia., Horáček J; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.; Third Faculty of Medicine, Charles University, Prague, Czechia., Páleníček T; Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.; Third Faculty of Medicine, Charles University, Prague, Czechia.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2023 Mar 09; Vol. 14, pp. 1120419. Date of Electronic Publication: 2023 Mar 09 (Print Publication: 2023).
DOI:	10.3389/fphar.2023.1120419
Abstrakt:	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. Competing Interests: TP and JH declare to have shares in “Psyon s.r.o.,” and in “Společnost pro podporu neurovědního výzkumu s.r.o.” They founded “PSYRES–Psychedelic Research Foundation”. TP also reports consulting fees from GH Research and CB21-Pharma outside the submitted work. TP and JH are involved in Compass Pathways trials with psilocybin and MAPS clinical trial with MDMA outside the submitted work. (Copyright © 2023 Syrová, Šíchová, Danda, Lhotková, Jorratt, Pinterová-Leca, Vejmola, Olejníková-Ladislavová, Hájková, Kuchař, Horáček and Páleníček.)
Databáze:	MEDLINE
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