神经药理学报

神经药理学报 ›› 2023, Vol. 13 ›› Issue (3): 21-.DOI: 10.3969/j.issn.2095-1396.2023.03.003

• 研究论文 • 上一篇    下一篇

一种新型抗精神病药物—哌马色林的体内药效评价

于民权，徐祥清，赵松，邱印利，赵义   

  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，中国
  • 出版日期:2023-06-26 发布日期:2024-05-09

In Vivo Efficacy Evaluation of Pimavanserin, A New Antipsychotic Drug

YU Min-quan, XU Xiang-qing, ZHAO Song, QIU Yin-li, ZHAO Yi   

  1. Jiangsu Nhwa Pharmaceutical Co., Ltd; Jiangsu Provincial Key Laboratory of CNS Drugs, Xuzhou, 221000, China
  • Online:2023-06-26 Published:2024-05-09

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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和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和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。

关键词: 哌马色林, 帕金森精神病, DOI, 5-HT2A

Abstract:

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-dibenzo[a,d]cyclohepten-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) significantlyinhibited DOI-induced head shaking behavior in mice (P < 0.05 or P < 0.001), and the ED50 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 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 ED50 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.

Key words: pimavanserin, Parkinsonian psychosis, DOI, 5-HT2A