探索Flavoxate及其类似物对两个化物通道和神经元作用潜力的选择性抑制作用
Gaohua Zhang1,2, Anmin Zhou1,2, Junjiang Liu1,2
1School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
弗拉沃克萨特可选择性地抑制体积调节的离子通道 (VRACs),并抑制神经元中的动作潜能激发,这表明神经病痛治疗的潜力. 它的结构类型显示较少的VRAC选择性,但也抑制神经元活动.
科学领域:
- 离子通道药理学 离子通道药理学
- 神经科学是一个神经科学.
- 疼痛研究 疼痛研究
背景情况:
- 量调节的离子通道 (VRAC) 和TMEM16A激活化通道 (CaCC) 是具有重叠功能的重要离子通道.
- 目前,缺乏针对VRACs和TMEM16A/CaCCs的特定抑制剂.
- 弗拉沃沙特已经显示了初步的VRAC抑制活性.
研究的目的:
- 调查弗拉沃沙特及其类型,MFCA和3-甲基弗拉对VRACs和TMEM16A/CaCCs的特定抑制作用.
- 探索这些黄类药物对背脊根结节神经元 (DRG) 激发动能 (AP) 的影响.
主要方法:
- 补丁电生理学被用来测量VRAC和TMEM16A/CaCC电流.
- 使用电流记录来评估对DRG神经元AP发射的影响.
- 分析了剂量反应关系,以确定IC50值.
主要成果:
- 弗拉沃沙特在VRAC抑制方面表现出高的疗效和选择性 (78%的抑制在30μM,IC50 = 1.8μM),对TMEM16A/CaCCs的影响很小.
- MFCA和3-甲基黄显示出较弱的VRAC抑制和中度的TMEM16A/CaCC抑制.
- 这三种化合物都显著抑制了DRG神经元中AP的激发.
结论:
- 弗拉沃沙特是一种强效和选择性的VRAC抑制剂,而8-替代剂对这种选择性至关重要.
- 黄类核心结构有助于抑制AP发射,这表明它在止痛作用中发挥了作用.
- 弗拉沃沙特通过抑制VRACs和神经元刺激性来作为神经病痛治疗剂具有前景.
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