TY - JOUR

T1 - Chronic Behavioral and Neurochemical Effects of Four Novel N-Benzyl-2-phenylethylamine Derivatives Recently Identified as “Psychoactive” in Adult Zebrafish Screens

AU - Ilyin, Nikita P.

AU - Nabiullin, Arslan D.

AU - Kozlova, Anna D.

AU - Kupriyanova, Olga V.

AU - Shevyrin, Vadim A.

AU - Gloriozova, Tatyana

AU - Filimonov, Dmitry

AU - Lagunin, Alexey

AU - Galstyan, David S.

AU - Kolesnikova, Tatiana O.

AU - Mor, Mikael S.

AU - Efimova, Evgeniya V.

AU - Poroikov, Vladimir

AU - Yenkoyan, Konstantin B.

AU - de Abreu, Murilo S.

AU - Demin, Konstantin A.

AU - Kalueff, Allan V.

N1 - Chronic Behavioral and Neurochemical Effects of Four Novel N-Benzyl-2-phenylethylamine Derivatives Recently Identified as "Psychoactive" in Adult Zebrafish Screens. ACS Chem Neurosci. 2024 May 15;15(10):2006-2017. doi: 10.1021/acschemneuro.4c00017. 

PY - 2024/4/29

Y1 - 2024/4/29

N2 - 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.

AB - 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.

KW - behavior

KW - in silico drug activity

KW - novel compounds

KW - psychopharmacology

KW - zebrafish

UR - https://www.mendeley.com/catalogue/94d15f2a-7e9c-3ef9-a737-d059538a41a4/

U2 - 10.1021/acschemneuro.4c00017

DO - 10.1021/acschemneuro.4c00017

M3 - Article

VL - 15

SP - 2006

EP - 2017

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 10

ER -