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517类似地阻断表达TRPV1的细胞中的辣椒素,质子和热诱导的内向电流。 AMG 517抑制大鼠背根神经节神经元中辣椒素对天然TRPV1的活化,IC50值为0.68±0.2 nM。 AMG 517是大鼠和人TRPV1的竞争性拮抗剂,解离常数(Kb)值分别为4.2和6.2 nM [2]。",{"key":237,"value":238},"体内研究","AMG 517显示在啮齿动物“靶向”生化挑战模型(辣椒素诱导的退缩,ED50 = 0.33mg\u002Fkg口服)中有效,并且在炎性疼痛模型中是抗痛觉过敏的(CFA诱导的热痛觉过敏,MED = 0.83 mg\u002Fkg,po)[1] .AMG 517的最低有效剂量为0.3 mg\u002Fkg,相应的血浆浓度为90 ng\u002FmL。口服施用AMG 517在CFA注射后21小时以剂量依赖性方式逆转建立的热痛觉过敏。 AMG 517在啮齿动物,狗和猴子中引起短暂的高温。 AMG 517以陡峭的剂量依赖性方式诱导高热,0.3,1和3mg\u002Fkg分别与体温升高0.5,0.6和1.6℃相关。用所有剂量的AMG 517治疗的大鼠的体温在10到20小时内回到基线[2]。",{"key":240,"value":241},"动物实验","大鼠：在完全适应测试设备和范例多天后，通过测量雄性Sprague-Dawley大鼠的缩爪潜伏期来评估CFA诱导的热痛觉过敏。在CFA注射后21小时（50μL，0.1％），给动物（po）施用AMG 517或AMG8163，剂量范围为0.001至30mg \u002F kg，体积为5mL \u002F kg。药物给药后2小时（CFA注射后23小时），通过完全不知道治疗条件的研究者使用改良的Hargreaves热箱测量缩爪潜伏期[2]。",{"key":243,"value":244},"参考文献","[1].\nDoherty EM, et al. 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