5-HT_(1A)受体激动和5-HT重摄取抑制双靶标新药YL-0919在小鼠体内的组织分布

Tissue distribution of YL-0919,a novel dual-acting antidepressant with 5-HT_(1A) receptor agonist and serotonin reuptake inhibitor in mice

目的研究5-HT1A受体激动和5-HT重摄取抑制双靶标新药YL-0919在小鼠体内的组织分布特征。方法 15只雄性昆明小鼠随机分为3组,单剂量YL-0919(6 mg/kg)灌胃后,分别于2,5,60 min摘眼球取血,处死后解剖取组织。采用液相色谱串联质谱法测定YL-0919浓度。结果小鼠YL-0919灌胃后2 min即在小肠、胃和肝达到最高值,其他组织在给药后5 min浓度达到最高值,浓度由高到低依次为:小肠>胃>肝脏>脂肪>肾脏>肺脏>心脏>脾脏>血>脑>肌肉>睾丸,60 min后各组织的药物浓度均降至较低水平。结论 YL-0919在小鼠体内的吸收和分布较快,药物入血后很快分布到体内各个组织中;药物在组织中的消除也较快,没有组织蓄积现象。

Objective To investigate the tissue distribution of YL-0919,a novel dual-acting antidepressant with 5-HT1A receptor agonist and serotonin reuptake inhibitor in mice.Methods Fifteen male Kunming mice were randomly divided into 3 groups.The samples of plasma and tissues were collected and YL-0919 was determined 2,5 and 60 min after oral administration of 6 mg·kg-1.LC-MS/MS method was established to determine YL-0919 in the tissues of mice.Results YL-0919 was orally administered to mice and the concentration of drugs reached the peak in the intestine,stomach and liver after 2 minutes and in other tissues after 5 minutes,respectively.The organs were listed in the order of the concentration of YL-0919：intestine,stomach,liver,fat,kidney,lung,heart,spleen,plasma,brain,muscle and testis.Concentration of YL-0919 in the tissues decreased to a very low level after 60 minutes.Conclusion YL-0919 can be quickly absorbed,distributed and eliminated after oral administration in mice and no concentration accumulation is observed in the tissues.