评估 fraxin 的镇静活性:体内方法以及受体结合亲和力和与 GABA 能系统的分子相互作用。

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-08-17 DOI:10.1002/ddr.22250
Sonaly Akter Mukty, Rubel Hasan, Md. Shimul Bhuia, Anik Kumar Saha, Umme Sadea Rahman, Mst Muslima Khatun, Sumaya Akter Bithi, Siddique Akber Ansari, Irfan Aamer Ansari, Muhammad Torequl Islam
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引用次数: 0

摘要

失眠是一种难以入睡和/或保持睡眠的睡眠障碍。本研究旨在评估fraxin(FX)对硫喷妥钠(TS)诱导的睡眠小鼠的镇静作用。此外,还进行了一项分子对接研究,以探究这些作用的分子过程。该研究使用成年雄性瑞士白化小鼠,在不同组别内分别或联合给药 FX(10 和 20 毫克/千克,静脉注射)和地西泮(DZP)(2 毫克/千克),以检测它们的调节作用。30 分钟后,给接受治疗的小鼠注射(TS:20 毫克/千克,静脉注射)诱导睡眠。小鼠的睡眠开始时间和睡眠时长均由人工记录。此外,还进行了计算分析,以预测γ-氨基丁酸(GABA)受体在睡眠过程中的作用,并评估其药代动力学和毒性。结果表明,FX 延长了睡眠时间,缩短了入睡时间。当 FX 和 DZP 联合治疗时,显示出协同镇静作用。此外,FX 的结合亲和力为 -7.2 kcal/mol,而 DZP 为 -8.4 kcal/mol。对 FX 的药代动力学研究表明,它具有良好的药物相似性和较强的药代动力学特征。最终,FX 在小鼠模型中表现出强烈的镇静作用,这可能是通过与 GABAA 受体途径相互作用实现的。
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Assessment of sedative activity of fraxin: In vivo approach along with receptor binding affinity and molecular interaction with GABAergic system

Insomnia is a sleep disorder in which you have trouble falling and/or staying asleep. This research aims to evaluate the sedative effects of fraxin (FX) on sleeping mice induced by thiopental sodium (TS). In addition, a molecular docking study was conducted to investigate the molecular processes underlying these effects. The study used adult male Swiss albino mice and administered FX (10 and 20 mg/kg, i.p.) and diazepam (DZP) (2 mg/kg) either separately or in combination within the different groups to examine their modulatory effects. After a period of 30 min, the mice that had been treated were administered (TS: 20 mg/kg, i.p.) to induce sleep. The onset of sleep for the mice and the length of their sleep were manually recorded. Additionally, a computational analysis was conducted to predict the role of gamma-aminobutyric acid (GABA) receptors in the sleep process and evaluate their pharmacokinetics and toxicity. The outcomes indicated that FX extended the length of sleep and reduced the time it took to fall asleep. When the combined treatment of FX and DZP showed synergistic sedative action. Also, FX had a binding affinity of −7.2 kcal/mol, while DZP showed −8.4 kcal/mol. The pharmacokinetic investigation of FX demonstrated favorable drug-likeness and strong pharmacokinetic characteristics. Ultimately, FX demonstrated a strong sedative impact in the mouse model, likely via interacting with the GABAA receptor pathways.

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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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