Metabolic Brain Disease

, Volume 34, Issue 5, pp 1375–1384 | Cite as

The faster-onset antidepressant effects of hypidone hydrochloride (YL-0919)

  • Li-jun Sun
  • Li-ming Zhang
  • Dan Liu
  • Rui Xue
  • Yan-qin Liu
  • Lei Li
  • Ying Guo
  • Chao Shang
  • Jun-qi Yao
  • You-zhi ZhangEmail author
  • Yun-feng LiEmail author
Original Article


Hypidone hydrochloride (YL-0919), is a novel structural antidepressant candidate as a triple selective serotonin re-uptake inhibitor (SSRI), 5-HT1A partial agonist and 5-HT6 agonist. Here, we investigated the rapid onset antidepressant-like effects of YL-0919 and the possible mechanism in rats exposed to a chronic unpredictable stress (CUS) paradigm. In the CUS rats, it was found that fluoxetine (FLX, 10 mg/kg) treatment exerted antidepressant actions on 20-22d, while YL-0919 or vilazodone (VLZ, a dual 5-HT1A partial agonist and SSRI) administrated once daily exerted faster antidepressant-like behaviors [4 days in the sucrose preference test (SPT) and 6 days in the novelty suppressed feeding test (NSF)]. Thereafter, the serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels were reversed by treatment with YL-0919 for 7 days. Furthermore, YL-0919 treatment for 5 days reversed the brain derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling and the key synaptic proteins, such as post-synaptic density (PSD95), GluR1 and presynaptic protein synapsin1. Meanwhile, the dendritic complexity of pyramidal neurons in prefrontal cortex (PFC) were also increased in the CUS rats. These data suggest that YL-0919 exerts a faster antidepressant-like effect on behaviors and this effect maybe at least partially mediated by the BDNF-mTOR signaling related dendritic complexity increase in the PFC.


Hypidone hydrochloride Antidepressant Faster-onset Prefrontal cortex Dendritic complexity 



This work was supported by the National Key New Drug Creation Program of China (No.2017ZX09309012) and the National Natural Science Foundation of China (No.81773703).

Compliance with ethical standards

Conflict of interest

None of the authors had conflict of interest to declare.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Li-jun Sun
    • 1
  • Li-ming Zhang
    • 1
  • Dan Liu
    • 2
  • Rui Xue
    • 1
  • Yan-qin Liu
    • 1
  • Lei Li
    • 3
  • Ying Guo
    • 4
  • Chao Shang
    • 1
  • Jun-qi Yao
    • 1
  • You-zhi Zhang
    • 1
    Email author
  • Yun-feng Li
    • 1
    Email author
  1. 1.Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Institute of Pharmacology and ToxicologyBeijingChina
  2. 2.Central Blood Station of HengshuiHengshuiChina
  3. 3.Department of AnesthesiologyBeijing Chuiyangliu HospitalBeijingChina
  4. 4.Department of AnesthesiologyGeneral Hospital of PLABeijingChina

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