C-Jun N-Terminal Kinases Inhibition: A New Approach to the Regulation of Venlafaxine Pharmacokinetics

Q3 Pharmacology, Toxicology and Pharmaceutics

Jordan Journal of Pharmaceutical Sciences Pub Date : 2023-09-23 DOI:10.35516/jjps.v16i3.718

Gleb Zyuz`kov, Yuliya Zyuz`Kova, Olga Bryushinina, Nataliya Abdrashitova, Alexandr Lakeev, Darya Tsuran, Galina Frelikh, Vladimir Udut

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Abstract

The effect of the c-Jun N-terminal kinases (JNK) inhibitor 'IQ-1' on the pharmacokinetics of the antidepressant venlafaxine was studied. An acceleration of the metabolism of this psychotropic agent was revealed when a modifier of intracellular signal transduction was administered to experimental animals in vivo. The JNK blockade was accompanied by a decrease in the plasma level of the antidepressant without changes in the concentration of the pharmacologically active metabolite O-desmethylvenlafaxine. The results obtained indicate a modification of the pattern of venlafaxine biotransformation, involving a change in metabolic pathways with an increase in the formation of other metabolites, or a correction of its distribution in the body. The revealed properties of the JNK inhibitor can be used to develop fundamentally new approaches to improve the effectiveness of antidepressant therapy with venlafaxine within the framework of implementing the 'Strategy for Targeted Regulation of Xenobiotic Metabolism and Drug Pharmacokinetics'.

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C-Jun n端激酶抑制:文拉法辛药动学调控的新途径

研究了c-Jun n -末端激酶(JNK)抑制剂IQ-1对抗抑郁药文拉法辛药动学的影响。当一种细胞内信号转导调节剂被施用于实验动物体内时，发现这种精神药物的代谢加速。JNK阻断伴随着血浆抗抑郁药水平的下降，而药理活性代谢物o -去甲基文拉法辛的浓度没有变化。所获得的结果表明，文拉法辛生物转化模式的改变，涉及代谢途径的改变，其他代谢物的形成增加，或其在体内分布的纠正。JNK抑制剂所揭示的特性可用于在实施“外源代谢和药物药代动力学靶向调节策略”的框架内开发新的方法，以提高文拉法辛抗抑郁治疗的有效性。

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来源期刊

Jordan Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

1.70

自引率

0.00%

发文量

期刊介绍： The Jordan Journal of Pharmaceutical Sciences (JJPS) is a scientific, bi-annual, peer-reviewed publication that will focus on current topics of interest to the pharmaceutical community at large. Although the JJPS is intended to be of interest to pharmaceutical scientists, other healthy workers, and manufacturing processors will also find it most interesting and informative. Papers will cover basic pharmaceutical and applied research, scientific commentaries, as well as views, reviews. Topics on products will include manufacturing process, quality control, pharmaceutical engineering, pharmaceutical technology, and philosophies on all aspects of pharmaceutical sciences. The editorial advisory board would like to place an emphasis on new and innovative methods, technologies, and techniques for the pharmaceutical industry. The reader will find a broad range of important topics in this first issue.