目的 评价兼有5-HT1A受体激动和5-HT重摄取抑制双靶标化合物YL-0919的抗抑郁作用,并在靶标水平探讨其作用机制.方法和结果 在小鼠悬尾和小鼠强迫游泳实验中,YL-0919(1.25,2.5,5 mg/kg,ig)能够显著地缩短小鼠悬尾不动时间和游泳不动时间,5-HT1A受体拮抗剂WAY100635(0.3 mg/kg,sc)能够完全拮抗YL-0919(2.5 mg/kg,ig)在小鼠悬尾实验中的抗抑郁作用;在药物诱发抑郁模型上,YL-0919增强5-羟色氨酸(5-hydroxytryptophan,5-HTP,120 mg/kg,ip)诱导的小鼠甩头行为,但不能拮抗高剂量阿扑吗啡(16 mg/kg,sc)诱导的降温作用;YL-0919在抗抑郁有效剂量范围内对小鼠的自主活动性无显著性影响.结论 新型双靶标新药YL-0919具有明确的抗抑郁作用,此作用与激动5-HT1A受体,增强5-HT系统的功能有关.%Objective To investigate the antidepressant-like effect and possible mechanism of YL-0919, a novel dual-acting antidepressant with 5-HT1A receptor agonist and serotonin reuptake inhibitor. Methods and Results In the tail suspension test and forced swimming test in mice, YL-0919( 1. 25, 2. 5 and 5 mg/kg, ig )significantly decreased the immobility time. 5-HT1A receptor antagonist ( WAY100635 , 0. 3 mg/kg, sc ) could completely prevent the antidepressant-like effect in the tail suspension test. In the 5-hydroxytryptophan ( 5-HTP,120 mg/kg, ip ) potentiation test, YL-0919 significantly increased the symptom of head-twitches induced by 5-HTP. However, YL-0919 had no significant effect on the apomorphine (16 mg/kg,sc )induced hypothermia or the locomotor activity in mice. Conclusion YL-0919 produces reliable antidpres-sant-like effect, which may be attributed to the activation of 5-HT1A receptor and the potentiation of 5-HT system.
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