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

Kateřina Syrová; Klára Šíchová; Hynek Danda; Eva Lhotková; Pascal Jorratt; Nikola Pinterová-Leca; Čestmír Vejmola; Lucie Olejníková-Ladislavová; Kateřina Hájková; Martin Kuchař; Jiří Horáček; Tomáš Páleníček

doi:10.3389/fphar.2023.1120419

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

Front Pharmacol. 2023 Mar 9:14:1120419. doi: 10.3389/fphar.2023.1120419. eCollection 2023.

Authors

Kateřina Syrová^{1

2}, Klára Šíchová¹, Hynek Danda^{1

2}, Eva Lhotková¹, Pascal Jorratt^{1

2}, Nikola Pinterová-Leca^{1

2}, Čestmír Vejmola^{1

2}, Lucie Olejníková-Ladislavová^{1

2}, Kateřina Hájková³, Martin Kuchař^{1

3}, Jiří Horáček^{1

2}, Tomáš Páleníček^{1

2}

Affiliations

¹ Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia.
² Third Faculty of Medicine, Charles University, Prague, Czechia.
³ Forensic Laboratory of Biologically Active Compounds, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czechia.

Abstract

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.

Keywords: 2C-B-Fly-NBOMe; NBOMe series; new psychoactive substance; pharmacokinetics; prepulse inhibition; thermoregulation.

Grants and funding

This work was supported by grant from the Czech Science Foundation (project 20-25349S), Czech Health Research Council (project NU21-04-00307), Long-term conceptual development of research organization (RVO 00023752), Ministry of the interior of the Czech Republic (project VK01010212), Specific University Research, Czech Ministry of Education, Youth and Sports (project 260533/SVV/2022), programme Cooperatio, Neuroscience Charles University and private funds obtained via Foundation for Psychedelic Research (https://psyres.eu).