期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 174, 期 9, 页码 769-780出版社
WILEY
DOI: 10.1111/bph.13675
关键词
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资金
- National Natural Science Foundation of China [81102423, 81302761, 81001653, 81173036]
- Beijing Natural Science Foundation [7164290]
Background and purposeOur previous studies revealed that hypidone hydrochloride (YL-0919), which acts as a selective 5-HT (serotonin) reuptake inhibitor (SSRI) and displays partial 5-HT1A 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. Experimental approachWe first investigated the target profile of YL-0919 using [S-35]-GTPS 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. Key resultsData from the present study demonstrated that YL-0919 displays partial 5-HT1A 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. Conclusions and implicationsThese data suggest that YL-0919 is probably a fast-onset potent antidepressant with few side effects.
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