Chronic Behavioral and Neurochemical Effects of Four Novel N -Benzyl-2-phenylethylamine Derivatives Recently Identified as "Psychoactive" in Adult Zebrafish Screens.

Autor: Ilyin NP; Almazov National Medical Research Centre, St. Petersburg 197341, Russia.; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia., Nabiullin AD; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia., Kozlova AD; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia., Kupriyanova OV; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.; Kazan State Medical University, Kazan 420012, Russia., Shevyrin VA; Institute of Chemical Engineering, Ural Federal University, 19 Mira Str. ,Ekaterinburg 620002, Russia., Gloriozova T; Institute of Biomedical Chemistry, Pogodinskaya str., 10, bldg. 8 ,Moscow 119121, Russia., Filimonov D; Institute of Biomedical Chemistry, Pogodinskaya str., 10, bldg. 8 ,Moscow 119121, Russia., Lagunin A; Institute of Biomedical Chemistry, Pogodinskaya str., 10, bldg. 8 ,Moscow 119121, Russia., Galstyan DS; Almazov National Medical Research Centre, St. Petersburg 197341, Russia.; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia., Kolesnikova TO; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia.; Neuroscience Laboratory, Cobrain Center, Yerevan State Medical University after Mkhitar Heratsi, Yerevan 0025, Armenia., Mor MS; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia., Efimova EV; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia., Poroikov V; Institute of Biomedical Chemistry, Pogodinskaya str., 10, bldg. 8 ,Moscow 119121, Russia., Yenkoyan KB; Neuroscience Laboratory, Cobrain Center, Yerevan State Medical University after Mkhitar Heratsi, Yerevan 0025, Armenia.; Biochemistry Department, Yerevan State Medical University after Mkhitar Heratsi, Yerevan 0025, Armenia., de Abreu MS; Graduate Program in Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre 900050, Brazil., Demin KA; Almazov National Medical Research Centre, St. Petersburg 197341, Russia.; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia., Kalueff AV; Almazov National Medical Research Centre, St. Petersburg 197341, Russia.; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia.; Neurobiology Program, Sirius University of Science and Technology, Sochi 354340, Russia.; Suzhou Key Laboratory of Neurobiology and Cell Signalling, Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China.
Jazyk: angličtina
Zdroj: ACS chemical neuroscience [ACS Chem Neurosci] 2024 May 15; Vol. 15 (10), pp. 2006-2017. Date of Electronic Publication: 2024 Apr 29.
DOI: 10.1021/acschemneuro.4c00017
Abstrakt: Potently affecting human and animal brain and behavior, hallucinogenic drugs have recently emerged as potentially promising agents in psychopharmacotherapy. Complementing laboratory rodents, the zebrafish ( Danio rerio ) is a powerful model organism for screening neuroactive drugs, including hallucinogens. Here, we tested four novel N -benzyl-2-phenylethylamine (NBPEA) derivatives with 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -F, -Cl, and -OCF 3 substitutions in the ortho position of the phenyl ring of the N -benzyl moiety (34H-NBF, 34H-NBCl, 24H-NBOMe(F), and 34H-NBOMe(F)), assessing their behavioral and neurochemical effects following chronic 14 day treatment in adult zebrafish. While the novel tank test behavioral data indicate anxiolytic-like effects of 24H-NBOMe(F) and 34H-NBOMe(F), neurochemical analyses reveal reduced brain norepinephrine by all four drugs, and (except 34H-NBCl) - reduced dopamine and serotonin levels. We also found reduced turnover rates for all three brain monoamines but unaltered levels of their respective metabolites. Collectively, these findings further our understanding of complex central behavioral and neurochemical effects of chronically administered novel NBPEAs and highlight the potential of zebrafish as a model for preclinical screening of small psychoactive molecules.
Databáze: MEDLINE