title: Neurochemical and behavioural effects of hypidone hydrochloride (YL-0919): a novel combined selective 5-HT reuptake inhibitor and partial 5-HT1Aagonist.
abstract: Our previous studies revealed that hypidone hydrochloride (YL-0919), which acts as a selective 5-HT (serotonin) reuptake inhibitor (SSRI) and displays partial 5-HT1Areceptor agonist properties, exerts a significant antidepressant effect in various animal models. The aim of present research was to further investigate the pharmacology of YL-0919.
  
  
  
  We first investigated the target profile of YL-0919 using [35S]-GTPγS binding and microdialysis. To determine whether the 5-HT or noradrenergic systems are involved in the antidepressant-like effect of YL-0919, the 5-hydroxytryptophan (5-HTP)-induced head-twitch test and antagonism with a high dose of apomorphine were performed. Using the learned helplessness paradigm, the novelty suppressed feeding test, the Vogel-type conflict and elevated plus-maze test, we further verified the antidepressant-like and anxiolytic-like effects of YL-0919. The effects of YL-0919 on hippocampal long-term potentiation (LTP) and sexual behaviour were also evaluated.
  
  
  
  Data from the present study demonstrated that YL-0919 displays partial 5-HT1Areceptor agonist properties, producing a greater impact on extracellular 5-HT levels than a conventional SSRI (fluoxetine), as well as significant antidepressant and anxiolytic effects. Furthermore, YL-0919 treatment rapidly influenced the synaptic plasticity (enhancing LTP) of rats. Finally, at doses close to those producing antidepressant-like effects, YL-0919 did not result in a marked inhibition of sexual function.
  
  
  
  These data suggest that YL-0919 is probably a fast-onset potent antidepressant with few side effects.
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhang
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.|Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.|College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
authors.forename: Yu-Lu
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Xiao-Xu
authors.initials: XX
authors.lastname: Hu
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Ran
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Yan-Qin
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: You-Zhi
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Ri-Fang
authors.initials: RF
authors.lastname: Yang
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Li
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology; D000928:Antidepressive Agents / Q000378:metabolism* / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D054333:Drug Partial Agonism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017551:Microdialysis / Q000379:methods; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D011728:Pyridones / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000378:metabolism* / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D010880:Piperidines; D011728:Pyridones; D044282:Receptor, Serotonin, 5-HT1A; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C000592342:1-(1-benzyl-4-hydroxypiperidin-4-ylmethyl)-2(1H)-pyridinone