Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 6;13(13):1902-1922.
doi: 10.1021/acschemneuro.2c00123. Epub 2022 Jun 7.

Acute behavioral and Neurochemical Effects of Novel N-Benzyl-2-Phenylethylamine Derivatives in Adult Zebrafish

Konstantin A Demin  1   2 , Olga V Kupriyanova  3   4 , Vadim A Shevyrin  5 , Ksenia A Derzhavina  1   2 , Nataliya A Krotova  1   2 , Nikita P Ilyin  1   2 , Tatiana O Kolesnikova  1   6 , David S Galstyan  1   7 , Yurii M Kositsyn  1 , Abubakar-Askhab S Khaybaev  2 , Maria V Seredinskaya  1 , Yaroslav Dubrovskii  2   8   9 , Raziya G Sadykova  4 , Maria O Nerush  2 , Mikael S Mor  1 , Elena V Petersen  10 , Tatyana Strekalova  11 , Evgeniya V Efimova  1 , Savelii R Kuvarzin  1 , Konstantin B Yenkoyan  12   13 , Dmitrii V Bozhko  14 , Vladislav O Myrov  14 , Sofia M Kolchanova  14 , Aleksander I Polovian  14 , Georgii K Galumov  14 , Allan V Kalueff  1   2   15   16   10   13   17
Affiliations

Acute behavioral and Neurochemical Effects of Novel N-Benzyl-2-Phenylethylamine Derivatives in Adult Zebrafish

Konstantin A Demin et al. ACS Chem Neurosci. .

Abstract

Hallucinogenic drugs potently affect brain and behavior and have also recently emerged as potentially promising agents in pharmacotherapy. Complementing laboratory rodents, the zebrafish (Danio rerio) is a powerful animal model organism for screening neuroactive drugs, including hallucinogens. Here, we test a battery of ten novel N-benzyl-2-phenylethylamine (NBPEA) derivatives with the 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -OCH3, -OCF3, -F, -Cl, and -Br substitutions in the ortho position of the phenyl ring of the N-benzyl moiety, assessing their acute behavioral and neurochemical effects in the adult zebrafish. Overall, substitutions in the Overall, substitutions in the N-benzyl moiety modulate locomotion, and substitutions in the phenethylamine moiety alter zebrafish anxiety-like behavior, also affecting the brain serotonin and/or dopamine turnover. The 24H-NBOMe(F) and 34H-NBOMe(F) treatment also reduced zebrafish despair-like behavior. Computational analyses of zebrafish behavioral data by artificial intelligence identified several distinct clusters for these agents, including anxiogenic/hypolocomotor (24H-NBF, 24H-NBOMe, and 34H-NBF), behaviorally inert (34H-NBBr, 34H-NBCl, and 34H-NBOMe), anxiogenic/hallucinogenic-like (24H-NBBr, 24H-NBCl, and 24H-NBOMe(F)), and anxiolytic/hallucinogenic-like (34H-NBOMe(F)) drugs. Our computational analyses also revealed phenotypic similarity of the behavioral activity of some NBPEAs to that of selected conventional serotonergic and antiglutamatergic hallucinogens. In silico functional molecular activity modeling further supported the overlap of the drug targets for NBPEAs tested here and the conventional serotonergic and antiglutamatergic hallucinogens. Overall, these findings suggest potent neuroactive properties of several novel synthetic NBPEAs, detected in a sensitive in vivo vertebrate model system, the zebrafish, raising the possibility of their potential clinical use and abuse.

Keywords: AI-phenotyping; behavior; in silico drug activity; novel compounds; psychopharmacology; zebrafish.

PubMed Disclaimer

Publication types

LinkOut - more resources