体内
等温滴定量热法
化学
药理学
芬太尼
甲基苯丙胺
赫尔格
生物相容性
生物物理学
生物化学
医学
有机化学
生物技术
生物
钾通道
作者
Adam T. Brockett,Weijian Xue,David King,Chun‐Lin Deng,Canjia Zhai,Malcolm D. Shuster,Shivangi Rastogi,Volker Briken,Matthew R. Roesch,Lyle Isaacs
出处
期刊:Chem
[Elsevier]
日期:2023-04-01
卷期号:9 (4): 881-900
被引量:9
标识
DOI:10.1016/j.chempr.2022.11.019
摘要
Pillar[6]MaxQ (P6AS) functions as an in vivo sequestration agent for methamphetamine and fentanyl. We use 1H NMR, isothermal titration calorimetry, and molecular modelling to deduce the geometry and strength of the P6AS•drug complexes. P6AS forms tight complexes with fentanyl (Kd=9.8 nM), PCP (17.1 nM), MDMA (25.5 nM), mephedrone (52.4 nM), and methamphetamine (101 nM). P6AS has good in vitro biocompatibility according to MTS metabolic, Adenylate Kinase cell death, and hERG ion channel inhibition assays, and the Ames fluctuation test. The no observed adverse effect level for P6AS is 45 mg/kg. The hyperlocomotion of mice treated with methamphetamine (0.5 mg/kg) can be ameliorated by treatment with P6AS (35.7 mg/kg) 5-minutes later, whereas the hyperlocomotion of mice treated with fentanyl (0.1 mg/kg) can be controlled by treatment with P6AS (5 mg/kg) up to 15-minutes later. P6AS has significant potential for development as a broad spectrum in vivo sequestration agent.
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