The study aimed to examine the potential of two novel
vasopressin V1B receptor antagonists,
TASP0233278 and TASP0390325, in treating
depression and
anxiety disorders. The research involved in vitro analysis of the antagonists' profiles and an investigation into TASP0390325's impact on plasma adrenocorticotropic hormone (ACTH) levels, which are elevated by corticotropin-releasing factor (CRF) and
desmopressin (dDAVP). Additionally, the study explored the antidepressant and anxiolytic effects of TASP0233278 and TASP0390325 in various animal models.
Key findings revealed that both TASP0233278 and TASP0390325 demonstrated high affinity and strong antagonistic activity towards V1B receptors. TASP0390325, when administered orally, was found to counteract the CRF/dDAVP-induced rise in plasma ACTH levels in rats, suggesting its ability to block the anterior pituitary V1B receptor in vivo. Furthermore, both compounds displayed antidepressant properties in two depression models: the forced swimming test and the olfactory bulbectomy model. TASP0233278 notably improved depressive-like behavior in a corticosterone-induced model, which is typically resistant to currently available antidepressants. The study also highlighted the anxiolytic effects of TASP0233278 and TASP0390325 across multiple
anxiety models, including social interaction, elevated plus-maze, stress-induced
hyperthermia, separation-induced ultrasonic vocalization, and
sodium lactate-induced
panic-like responses in panic-prone rats.
In conclusion, TASP0233278 and TASP0390325 emerged as effective, orally bioavailable V1B receptor antagonists with demonstrated antidepressant and anxiolytic properties in rodent studies.
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.

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.

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.

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