Acute behavioral and Neurochemical Effects of Novel N-Benzyl-2-Phenylethylamine Derivatives in Adult ZebrafishClick to copy article linkArticle link copied!
- Konstantin A. Demin*Konstantin A. Demin*Email: [email protected]Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaAlmazov National Medical Research Centre, St. Petersburg 197341, RussiaMore by Konstantin A. Demin
- Olga V. KupriyanovaOlga V. KupriyanovaInstitute of Fundamental Medicine and Biology, Kazan Volga Region Federal University, Kazan 420008, RussiaKazan State Medical University, Kazan 420012, RussiaMore by Olga V. Kupriyanova
- Vadim A. Shevyrin*Vadim A. Shevyrin*Email: [email protected]Institute of Chemistry and Technology, Ural Federal University, 19 Mira Str., Ekaterinburg 620002, RussiaMore by Vadim A. Shevyrin
- Ksenia A. DerzhavinaKsenia A. DerzhavinaInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaAlmazov National Medical Research Centre, St. Petersburg 197341, RussiaMore by Ksenia A. Derzhavina
- Nataliya A. KrotovaNataliya A. KrotovaInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaAlmazov National Medical Research Centre, St. Petersburg 197341, RussiaMore by Nataliya A. Krotova
- Nikita P. IlyinNikita P. IlyinInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaAlmazov National Medical Research Centre, St. Petersburg 197341, RussiaMore by Nikita P. Ilyin
- Tatiana O. KolesnikovaTatiana O. KolesnikovaInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaNeurobiology Program, Sirius University of Science and Technology, Sochi 354340, RussiaMore by Tatiana O. Kolesnikova
- David S. GalstyanDavid S. GalstyanInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaLaboratory of Preclinical Bioscreening, Granov Russian Research Center of Radiology and Surgical Technologies, Ministry of Healthcare of Russian Federation, Pesochny 197758, RussiaMore by David S. Galstyan
- Yurii M. KositsynYurii M. KositsynInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaMore by Yurii M. Kositsyn
- Abubakar-Askhab S. KhaybaevAbubakar-Askhab S. KhaybaevAlmazov National Medical Research Centre, St. Petersburg 197341, RussiaMore by Abubakar-Askhab S. Khaybaev
- Maria V. SeredinskayaMaria V. SeredinskayaInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaMore by Maria V. Seredinskaya
- Yaroslav DubrovskiiYaroslav DubrovskiiAlmazov National Medical Research Centre, St. Petersburg 197341, RussiaInstitute of Chemistry, St. Petersburg State University, St. Petersburg 199034, RussiaSt. Petersburg State Chemical Pharmaceutical University, St. Petersburg 197022, RussiaMore by Yaroslav Dubrovskii
- Raziya G. Sadykova
- Maria O. NerushMaria O. NerushAlmazov National Medical Research Centre, St. Petersburg 197341, RussiaMore by Maria O. Nerush
- Mikael S. MorMikael S. MorInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaMore by Mikael S. Mor
- Elena V. PetersenElena V. PetersenMoscow Institute of Physics and Technology, Moscow 141701, RussiaMore by Elena V. Petersen
- Tatyana StrekalovaTatyana StrekalovaMaastricht University, NL Postbus 616, Maastricht 62, NetherlandsMore by Tatyana Strekalova
- Evgeniya V. EfimovaEvgeniya V. EfimovaInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaMore by Evgeniya V. Efimova
- Savelii R. KuvarzinSavelii R. KuvarzinInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaMore by Savelii R. Kuvarzin
- Konstantin B. YenkoyanKonstantin B. YenkoyanNeuroscience Laboratory, COBRAIN Center, M. Heratsi Yerevan State Medical University, Yerevan AM 0025, ArmeniaCOBRAIN Scientific Educational Center for Fundamental Brain Research, Yerevan AM 0025, ArmeniaMore by Konstantin B. Yenkoyan
- Dmitrii V. Bozhko
- Vladislav O. Myrov
- Sofia M. Kolchanova
- Aleksander I. PolovianAleksander I. PolovianZebraML, Inc., Houston 77001 Texas, United StatesMore by Aleksander I. Polovian
- Georgii K. Galumov
- Allan V. Kalueff*Allan V. Kalueff*Email: [email protected]. Phone: +1-240-899-9571.Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, RussiaAlmazov National Medical Research Centre, St. Petersburg 197341, RussiaUral Federal University, Ekaterinburg 620075, RussiaGranov Russian Research Center of Radiology and Surgical Technologies, Ministry of Healthcare of Russian Federation, Pesochny 197758, RussiaMoscow Institute of Physics and Technology, Moscow 141701, RussiaCOBRAIN Scientific Educational Center for Fundamental Brain Research, Yerevan AM 0025, ArmeniaScientific Research Institute of Neuroscience and Medicine, Novosibirsk, 630117, RussiaMore by Allan V. Kalueff
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.
Cited By
This article is cited by 2 publications.
- 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. Chronic Behavioral and Neurochemical Effects of Four Novel N-Benzyl-2-phenylethylamine Derivatives Recently Identified as “Psychoactive” in Adult Zebrafish Screens. ACS Chemical Neuroscience 2024, 15
(10)
, 2006-2017. https://doi.org/10.1021/acschemneuro.4c00017
- Binjie Wang, Jiale Chen, Zhong Sheng, Wanting Lian, Yuanzhao Wu, Meng Liu. Embryonic exposure to fentanyl induces behavioral changes and neurotoxicity in zebrafish larvae. PeerJ 2022, 10 , e14524. https://doi.org/10.7717/peerj.14524
Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.
Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.
The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.