Acute behavioral and Neurochemical Effects of Novel N -Benzyl-2-Phenylethylamine Derivatives in Adult Zebrafish
Konstantin A. Demin, Olga V. Kupriyanova, Вадим А. Шевырин, Ksenia A. Derzhavina, Nataliya A. Krotova, Nikita P. Ilyin, Tatiana O. Kolesnikova, David S. Galstyan, Yurii M. Kositsyn, Abubakar-Askhab S. Khaybaev, Maria Seredinskaya, Yaroslav A. Dubrovskii, Raziya G. Sadykova, Maria O. Nerush, Mikael S. Mor, Elena V. Petersen, Tatyana Strekalova, Evgeniya Efimova, Savelii R. Kuvarzin, Konstantin B. Yenkoyan, Dmitrii V. Bozhko, Vladislav Myrov, Sofia M. Kolchanova, Aleksander I. Polovian, Georgii K. Galumov, Allan V. Kalueff
ACS Chemical Neuroscience June 7, 2022 DOI: 10.1021/acschemneuro.2c00123 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult zebrafish |
| Interventions | 24H–NBOMe 34H–NBF 34H–NBBr 34H–NBCl 34H–NBOMe 24H–NBBr 24H–NBCl 24H–NBOMe(F) 34H–NBOMe(F)) |
| Topics | Mescaline Serotonin |
| Keywords | Neurochemical Hallucinogen Phenethylamine Zebrafish Anxiogenic Pharmacology Moiety Anxiolytic Stereochemistry Biochemistry Receptor |
| Citations | 20 |
| Key findings | Novel NBPEA derivatives modulate locomotion and anxiety-like behavior in zebrafish, with some compounds showing behavioral similarity to conventional serotonergic and antiglutamatergic hallucinogens. |
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.
Comparable studies
Other preclinical and animal studies on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Brain mechanisms of hallucinogens and entactogens Humans and rats | 2001 | Review | |
| Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology Zebrafish (Danio rerio) | 2012 | Experimental study | |
| Lysergic Acid Diethylamide- and Mescaline-Induced Attenuation of the Effect of Punishment in the Rat Rats | 1976 | Experimental study | |
| Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups Rats (trained to discriminate saline from LSD tartrate) and rat cortical and... | 1996 | In vivo drug discrimination assay and in vitro radioligand binding assay |
Citations in the library
Cited by 2
- Psychedelics and neuroregenerative medicine: Illuminating the potential of psychoplastogens for neurodevelopment and central nervous system repair Psychedelics September 8, 2026
- Chronic Behavioral and Neurochemical Effects of Four Novel N-Benzyl-2-phenylethylamine Derivatives Recently Identified as "Psychoactive" in Adult Zebrafish Screens. ACS Chemical Neuroscience April 29, 2024
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