新化合物130P4对迟发性运动障碍的作用  

Effect of New Compound 130P4 on Tardive Dyskinesia

作　　者：刘如梦 徐亚男 朱晓音[1] 田京伟[1] LIU Ru-meng;XU Ya-nan;ZHU Xiao-yin;TIAN Jing-wei(School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,China)

机构地区：[1]烟台大学药学院,分子药理和药物评价教育部重点实验室(烟台大学),新型制剂与生物技术药物研究山东省高校协同创新中心,山东烟台264005

出　　处：《烟台大学学报（自然科学与工程版）》2022年第1期55-59,共5页Journal of Yantai University(Natural Science and Engineering Edition)

摘　　要：本文旨在研究新的VMAT2抑制剂130P4对迟发性运动障碍的治疗作用。采用体外研究考察130P4对靶点VMAT2的亲和力,采用SD大鼠自主活动模型、眼睑下垂模型和催乳素分泌模型对130P4进行体内药效学评价。结果显示:130P4与VMAT2的亲和力高(K_(i)=1.38 nmol/L);130P4可剂量依赖性地降低大鼠自主活动,诱导大鼠眼睑下垂,和升高血清催乳素水平;等摩尔剂量下,130P4药效作用优于上市药物Valbenazine。综上所述,130P4与靶点亲和力高,在大鼠体内对VMAT2具有抑制作用,药效作用优于Valbenazine。To study the therapeutic effects of 130P4,a new inhibitor of VMAT2 on tardive dyskinesia,the affinity of 130P4 for the target VMAT2 is performed in in vitro radioligand binding assays.In addition,in vivo activity of 130P4 is assessed in locomotor activity model,palpebral ptosis model and prolactin secretion model.The results show that 130P4 displays a high affinity for VMAT2(K_(i) of 1.38 nmol/L).Oral administration of 130P4 decreases locomotor activity,induces palpebral ptosis,and increases serum prolactin levels in rats in dose dependent manner.At equimolar dose,effect of 130P4 is superior to that of the marketed drug valbenazine.In summary,130P4 has a high affinity for VMAT2 and inhibitory effects on VMAT2 in rats,therefore shows a better pharmacodynamic character than valbenazine.

关 键 词：VMAT2抑制剂 自主活动 眼睑下垂 催乳素分泌 

分 类 号：R964[医药卫生—药理学]