Exploring the Antidepressant Potential of ZBH2012001: A New Serotonin and Norepinephrine Reuptake Inhibitor

3 June 2024
The objective of this research was to assess the antidepressant properties of ZBH2012001, a newly developed agent with the potential to inhibit the reuptake of serotonin and norepinephrine. Various assays, including competitive binding, calcium flow, and cAMP detection, were utilized to measure the affinity of ZBH2012001 for serotonin and norepinephrine transporters, as well as its selectivity over dopamine transporters and other receptors. The study also evaluated the antidepressant efficacy of ZBH2012001 through behavioral tests such as the tail suspension test, forced swim test, and learned helplessness paradigm. Additionally, the pharmacokinetics and acute toxicity of the compound were examined.

Results showed that ZBH2012001 had moderate binding affinity for both serotonin and norepinephrine transporters, with Ki values of 35.3 ± 2.86 nM and 225 ± 26.0 nM, respectively, and did not affect dopamine transporters or other receptors. Behavioral tests demonstrated that ZBH2012001 had better antidepressant effects than the commonly used SNRI, duloxetine. The compound also displayed a 60.5% absolute bioavailability and an LD50 of 346 mg/kg in acute toxicity tests.

In conclusion, ZBH2012001 is a promising SNRI with enhanced antidepressant activity, lower toxicity, and a favorable pharmacokinetic profile compared to duloxetine, indicating its potential as a therapeutic agent for depression.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

图形用户界面, 文本, 应用程序, 电子邮件

描述已自动生成

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

图形用户界面, 文本, 应用程序, 电子邮件

描述已自动生成

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

图片包含 应用程序

描述已自动生成

Click on the image below to go directly to the Translational Medicine search interface.

图形用户界面, 文本, 应用程序, 电子邮件

描述已自动生成