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

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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.

Compliance with ethical standards. The study does not require the submission of a biomedical ethics committee opinion or other documents, as the study was conducted on fish embryos in accordance with SIS 33774-2016 “Testing chemicals that pose a danger to the environment. Acute toxicity of fish embryos (FET)”.

Author contribution. All co-authors made an equal contribution to the research and preparation of the article for publication.

Conflict of interests. The authors declare no conflict of interest. 

Funding. The study was not sponsored.

Received: December 27, 2022 / Accepted: May 26, 2023 / Published: June 30, 2023

About the authors

Alla Andreevna Volkova

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

Author for correspondence.
Email: noemail@neicon.ru

Кандидат фармацевтических наук, научный сотрудник ФГБУ «Российский центр судебно-медицинской экспертизы» МЗ РФ, 125284, Москва, Россия.

e-mail: himija@rc-sme.ru

Russian Federation

Roman Anatolievich Kalekin

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

Email: noemail@neicon.ru

Доктор фармацевтических наук, научный сотрудник ФГБУ «Российский центр судебно-медицинской экспертизы» МЗ РФ, 125284, Москва, Россия.

e-mail: himija@rc-sme.ru

Russian Federation

Alevtina Mikhailovna Orlova

FGBU “Russian Center of Forensic Medical Examination”

Email: himija@rc-sme.ru

Ph.D. in Pharmaceutical Sciences, Leading Researcher of Russian Center of Forensic Medical Examination, Moscow.

e-mail: himija@rc-sme.ru

Russian Federation

Albina Zakharovna Pavlova

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

Email: noemail@neicon.ru

Доктор биологических наук, научный сотрудник ФГБУ «Российский центр судебно-медицинской экспертизы» МЗ РФ, 125284, Москва, Россия.

e-mail: himija@rc-sme.ru

Russian Federation

Olga Genrikhovna Astashkina

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

Email: noemail@neicon.ru

Доктор медицинских наук, научный сотрудник ФГБУ «Российский центр судебно-медицинской экспертизы» МЗ РФ, 125284, Москва, Россия.

e-mail: himija@rc-sme.ru

Russian Federation

Andrey Leonidovich Pavlov

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

Email: noemail@neicon.ru

Врач, ГБУ г. Москвы «Центр реабилитации инвалидов «Царицыно»» Департамента труда и социальной защиты населения города Москвы, 117534, Москва, Россия.

e-mail: himija@rc-sme.ru

Russian Federation

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Copyright (c) 2023 Volkova A.A., Kalekin R.A., Orlova A.M., Pavlova A.Z., Astashkina O.G., Pavlov A.L.


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