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

Nikita P. Ilyin, Arslan D. Nabiullin, Anna D. Kozlova, Olga V. Kupriyanova, Vadim A. Shevyrin, Tatyana Gloriozova, Dmitry Filimonov, Alexey Lagunin, David S. Galstyan, Tatiana O. Kolesnikova, Mikael S. Mor, Evgeniya V. Efimova, Vladimir Poroikov, Konstantin B. Yenkoyan, Murilo S. de Abreu, Konstantin A. Demin*, Allan V. Kalueff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 −OCF3 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.

Original languageEnglish
Pages (from-to)2006-2017
Number of pages12
JournalACS Chemical Neuroscience
Volume15
Issue number10
DOIs
Publication statusPublished - 15 May 2024

Keywords

  • behavior
  • in silico drug activity
  • novel compounds
  • psychopharmacology
  • zebrafish

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