Репозиторий Университета

© 2021 Elsevier Inc. Introduction: Diazepam is a well-known psychoactive drug widely used worldwide for the treatment of anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, sleeplessness, agitation, and pre/post-operative sedation. It is part of the benzodiazepine family, substances known to primarily act by binding and enhancing gamma-aminobutyric acid (GABAA) receptors. The objective of the present work was to investigate the influence of short and medium-term diazepam exposures on neurotransmitters measured through targeted metabolomics using a zebrafish embryo model. Methods: Short-term (2.5 h) and medium-term (96 h) exposures to diazepam were performed at drug concentrations of 0.8, 1.6, 16, and 160 μg/L. Intervention groups were compared with a vehicle control group. Each group consisted of 20 zebrafish eggs/larvae. Metabolites related with neurotransmission were determined by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Results: Thirty-six compounds were quantified. Significantly increased tryptophan and serotonin concentrations were found in the intervention groups receiving higher doses of diazepam in 2.5 h exposure (p < 0.05 control versus intervention groups). Tyrosine concentrations were higher (p < 0.05) at higher concentrations in 2.5 h exposure, but lower (p < 0.05) at higher concentrations in 96 h exposure. Both phenylalanine and aspartic acid concentrations were higher (p < 0.05) at higher doses in 2.5 h and 96 h exposure. Conclusions: Short- and medium-term exposures to diazepam induce dose- and time-dependent metabolomic alterations associated with the serotonergic, dopaminergic/adrenergic, and aspartic acid neurotransmitter systems in zebrafish.

© 2021 Elsevier Inc. Introduction: Diazepam is a well-known psychoactive drug widely used worldwide for the treatment of anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, sleeplessness, agitation, and pre/post-operative sedation. It is part of the benzodiazepine family, substances known to primarily act by binding and enhancing gamma-aminobutyric acid (GABAA) receptors. The objective of the present work was to investigate the influence of short and medium-term diazepam exposures on neurotransmitters measured through targeted metabolomics using a zebrafish embryo model. Methods: Short-term (2.5 h) and medium-term (96 h) exposures to diazepam were performed at drug concentrations of 0.8, 1.6, 16, and 160 μg/L. Intervention groups were compared with a vehicle control group. Each group consisted of 20 zebrafish eggs/larvae. Metabolites related with neurotransmission were determined by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Results: Thirty-six compounds were quantified. Significantly increased tryptophan and serotonin concentrations were found in the intervention groups receiving higher doses of diazepam in 2.5 h exposure (p < 0.05 control versus intervention groups). Tyrosine concentrations were higher (p < 0.05) at higher concentrations in 2.5 h exposure, but lower (p < 0.05) at higher concentrations in 96 h exposure. Both phenylalanine and aspartic acid concentrations were higher (p < 0.05) at higher doses in 2.5 h and 96 h exposure. Conclusions: Short- and medium-term exposures to diazepam induce dose- and time-dependent metabolomic alterations associated with the serotonergic, dopaminergic/adrenergic, and aspartic acid neurotransmitter systems in zebrafish.

The tendency to anxiety is a characteristic feature of alcohol abusers, and anxiety can be a symptom of alcohol withdrawal as well as comorbid disorder. The frequent comorbidity of alcohol use disorders and anxiety is due to a number of reasons including general hereditary predisposition, mutual conditioning and similar pathogenesis. Pharmacological therapy of anxiety disorders in alcohol-dependent patients is carried out on the basis of general principles of anxiety treatment and involves the use of benzodiazepines, antidepressants and, in some cases, antipsychotics as second-line medicines.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This article provides a short history of the creation of hypnotics, examines their mechanisms of action, and conducts a comparative analysis of the main groups of hypnotics such as barbiturates, benzodiazepines, "nonbenzodiazepine" benzodiazepine receptor agonists, melatonin receptor agonists, orexin receptor antagonists, histamine H1-receptor antagonists.