The effect of zaleplon on metabolic changes in neurotransmitters and toxic effects in Danio fish

Author:

Volkova Alla Andreevna1,Kalekin Roman Anatolievich1,Orlova Alevtina Mikhailovna2,Pavlova Albina Zakharovna3,Astashkina Olga Genrikhovna4,Pavlov Andrey Leonidovich5

Affiliation:

1. FGBU “Russian Center of Forensic Medical Examination”; FGAOU VO “Peoples’ Friendship University of Russia”

2. FGBU “Russian Center of Forensic Medical Examination”

3. FGBU “Russian Center of Forensic Medical Examination”; FGBNU “Scientific Research Institute of Human Morphology named after Academician A.P. Avtsyn” Ministry of Education and Science of Russia

4. FGBU “Russian Center of Forensic Medical Examination”; GBUZ “Bureau of Forensic Medical Examination” of the Moscow Department of Health

5. FGBU “Russian Center of Forensic Medical Examination”; GBU of Moscow Center for Rehabilitation of disabled people “Tsaritsyno”

Abstract

Introduction. Z-drugs are a group of “non-benzodiazepine” drugs with the main mode of action regulating sleep behavior in humans through exposure to GABA receptors. There are reports indicating the toxic effects of overdose and abuse of zaleplon. However, information on the effect of Z-drugs on neurotransmitter levels is scarce. The aim of this study was to study the effect of zaleplon exposure on neurotransmitter levels in the larvae of Danio fish using targeted metabolomics. Material and methods. 4-hour exposure to zaleplon in concentrations of 0.1, 1.0, 10, 100 and 1000 μg/l was carried out on the larvae of Danio fish. Intervention groups were compared with control groups. Each group consisted of 20 larvae of Danio fish. Neurotransmitters and their metabolites were measured using high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS). Results. Twenty-two metabolites associated with neurotransmission were quantified. Significantly increased metabolites were tryptophan, serotonin, 5-hydroxyindolacetic acid, acetylserotonin, epinephrine and choline. Significantly reduced metabolites were 5-hydroxytryptophan, 5-methoxytryptamine, dopamine, normetanephrine, metanephrine, kynurenine, 3-hydroxykinurenine, anthranilic acid and gamma-aminobutyric acid. Limitation. When studying metabolic changes in neurotransmitters and toxic effects in Danio fish, the results of a group of 20 larvae were analyzed, which is a sufficient sample to state the results obtained. Conclusion. Exposure to zaleplon caused metabolic changes in the concentrations of neurotransmitters associated with most major neurotransmitter systems.

Publisher

Federal Scientific Center for Hygiene F.F.Erisman

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