一种新型抗精神病药物—哌马色林的体内药效评价  

In Vivo Efficacy Evaluation of Pimavanserin,A New Antipsychotic Drug

作　　者：于民权[1] 徐祥清[1] 赵松[1] 邱印利[1] 赵义 YU Min-quan;XU Xiang-qing;ZHAO Song;QIU Yin-li;ZHAO Yi(Jiangsu Nhwa Pharmaceutical Co.,Ltd,Jiangsu Provincial Key Laboratory of CNS Drugs,Xuzhou,221000,China)

机构地区：[1]江苏恩华药业股份有限公司,江苏省中枢神经药物研究重点实验室,徐州221000

出　　处：《神经药理学报》2023年第3期21-25,共5页Acta Neuropharmacologica

摘　　要：目的:研究5-HT2A受体反向激动剂哌马色林的体内药理学作用及抗精神病活性。方法:采用DOI(±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride)诱导小鼠甩头模型、DOI诱导大鼠前脉冲抑制(prepulse inhibition,PPI)损伤模型及MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)+MK-801{(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate)}诱导小鼠帕金森精神病(Parkinson′s disease psychosis,PDP)模型的影响,评估哌马色林体内药理学作用及抗精神病活性。结果:哌马色林(0.1、0.3、1、3 mg·kg^(-1))可显著抑制DOI诱导的小鼠甩头行为(P<0.05或P<0.001),哌马色林抑制小鼠甩头行为的ED50为0.20 mg·kg^(-1)。哌马色林3、10 mg·kg^(-1)可显著逆转DOI诱导大鼠PPI损伤(P<0.05或0.01),但在该剂量下对正常大鼠PPI无明显影响。哌马色林在3、10 mg·kg^(-1)时可显著减少MK-801诱导的PD小鼠高活动行为(P<0.05),哌马色林在该帕金森精神病模型上的ED50为2.86 mg·kg^(-1)。结论:哌马色林可能通过阻断脑内5-HT2A受体的功能,逆转DOI诱导的大鼠PPI损伤,并对MPTP+MK-801诱导小鼠PDP模型有显著的改善作用。Objective:To study the in vivo pharmacological effects and antipsychotic activity of pimavanserin,a 5-HT2A receptor inverse agonists.Methods:The in vivo pharmacological effects and antipsychotic activity of pimavanserin were evaluated by DOI induced head shaking model in mice,DOI induced prepulse inhibition(PPI)injury model in rats and MPTP(1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)+MK-801((+)-5-methyl-10,11-dihydro-5H-dibenzoLa,dJcyclohepten-5,10-imine maleate)induced parkinson's disease psychosis(PDP)model in mice.Results:Pimavanserin(0.1,0.3,1 and 3 mg·kg^(-1))significantly inhibited DOI-induced head shaking behavior in mice(P<0.05 or P<0.001),and the EDso of pimavanserin inhibited head shaking behavior in mice was 0.20 mg·kg^(-1).Pimavanserin 3 and 10 mg·kg^(-1)could significantly reverse DOI induced PPI injury in rats(P<0.05 or P<0.01),but had no significant effect on PPI in normal rats at this dose.At 3 and 10 mg·kg^(-1),pimavanserin significantly reduced the hyperactivity behavior induced by MK-801 in PD mice(P<0.05),and the EDso of pimavanserin in this PDP model was 2.86 mg·kg^(-1).Conclusion:Pimavanserin can reverse DOI induced PPI injury in rats by blocking the function of 5-HT2A receptor in the brain,and has a significant improvement effect on MPTP+MK-801 induced PDP model in mice.

关 键 词：哌马色林 帕金森精神病 DOI 5-HT2A 

分 类 号：R964[医药卫生—药理学]