Neurochemical and behavioural effects of hypidone hydrochloride (YL-0919): a novel combined selective 5-HT reuptake inhibitor and partial 5-HT 1A agonist

Our previous studies revealed that hypidone hydrochloride (YL-0919), which acts as a selective 5-HT (serotonin) reuptake inhibitor (SSRI) and displays partial 5-HT receptor agonist properties, exerts a significant antidepressant effect in various animal models. The aim of present research was to fur...

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Veröffentlicht in:British journal of pharmacology 2017-05, Vol.174 (9), p.769-780
Hauptverfasser: Zhang, Li-Ming, Wang, Xiao-Yun, Zhao, Nan, Wang, Yu-Lu, Hu, Xiao-Xu, Ran, Yu-Hua, Liu, Yan-Qin, Zhang, You-Zhi, Yang, Ri-Fang, Li, Yun-Feng
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container_end_page 780
container_issue 9
container_start_page 769
container_title British journal of pharmacology
container_volume 174
creator Zhang, Li-Ming
Wang, Xiao-Yun
Zhao, Nan
Wang, Yu-Lu
Hu, Xiao-Xu
Ran, Yu-Hua
Liu, Yan-Qin
Zhang, You-Zhi
Yang, Ri-Fang
Li, Yun-Feng
description Our previous studies revealed that hypidone hydrochloride (YL-0919), which acts as a selective 5-HT (serotonin) reuptake inhibitor (SSRI) and displays partial 5-HT receptor 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 [ S]-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-HT receptor 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.
doi_str_mv 10.1111/bph.13675
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The aim of present research was to further investigate the pharmacology of YL-0919. We first investigated the target profile of YL-0919 using [ S]-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-HT receptor agonist properties, producing a greater impact on extracellular 5-HT levels than a conventional SSRI (fluoxetine), as well as significant antidepressant and anxiolytic effects. 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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.</abstract><cop>England</cop><pmid>27882537</pmid><doi>10.1111/bph.13675</doi><tpages>12</tpages></addata></record>
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subjects Animals
Anti-Anxiety Agents - metabolism
Anti-Anxiety Agents - pharmacology
Antidepressive Agents - metabolism
Antidepressive Agents - pharmacology
Avoidance Learning - drug effects
Avoidance Learning - physiology
Dose-Response Relationship, Drug
Drug Partial Agonism
Female
Hippocampus - drug effects
Hippocampus - metabolism
Male
Mice
Mice, Inbred ICR
Microdialysis - methods
Piperidines - metabolism
Piperidines - pharmacology
Pyridones - metabolism
Pyridones - pharmacology
Rats
Rats, Sprague-Dawley
Rats, Wistar
Receptor, Serotonin, 5-HT1A - metabolism
Serotonin 5-HT1 Receptor Agonists - metabolism
Serotonin 5-HT1 Receptor Agonists - pharmacology
Serotonin Uptake Inhibitors - metabolism
Serotonin Uptake Inhibitors - pharmacology
Sexual Behavior, Animal - drug effects
Sexual Behavior, Animal - physiology
title Neurochemical and behavioural effects of hypidone hydrochloride (YL-0919): a novel combined selective 5-HT reuptake inhibitor and partial 5-HT 1A agonist
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