之间的协同作用对竞争对手在成人肌肉乙酰胆碱受体。

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刘米,迪尔格JP

之间的协同作用对竞争对手在成人肌肉乙酰胆碱受体。

8月Anesth。2008; 107(2): 525 - 33所示。doi: 10.1213 / ane.0b013e31817b4469。

PubMed ID

18633030 (在PubMed

]

文摘

背景:协同神经肌肉阻断作用与某些临床观察对烟碱乙酰胆碱受体(乙酰)的竞争对手。协同作用机制尚未阐明。我们测试的假设协同起源于一个微分选择性拮抗剂的成人乙酰两个配体结合位点。方法:我们表示乙酰BOSC23细胞。我们应用ACh有或没有对手外部补丁和测量在室温下宏观电流。我们决定集成电路(90)(+)筒箭毒碱,metocurine,泮库,维库,cisatracurium, rocuronium和阿曲库。15的组合两个对手,我们确定一个对手的集成电路(90)的集成电路(70)的第二个对手。我们建造isobolograms抑制90%。为单一的对手,我们测量含有抑制受体突变ε- delta-subunits确定网站选择性。结果:两双拮抗剂,metocurine + cisatracurium和cisatracurium +阿曲库添加剂抑制展出。 Ten combinations, including (+)-tubocurarine+ pancuronium and pancuronium+vecuronium, were highly synergistic such that the combination was two to three times more effective than expected for additivity. Three combinations were 1.5-1.6 times more effective than expected for additivity. Inhibition by (+)-tubocurarine and metocurine was sensitive to mutations in the epsilon-subunit only. Vecuronium was affected by the delta-subunit mutation only. Inhibition by other antagonists was decreased by mutations in either subunit. CONCLUSIONS: Many combinations of antagonists exhibited synergistic effects on adult human nAChR. Synergy was observed with structurally similar and dissimilar antagonists. The degree of synergy did not always correlate well with site specificity assayed with mutants. In some, but not all cases, the synergy at the receptor level correlated with clinical determinations of synergy. We conclude that the synergistic actions of muscle relaxants can be partially explained by direct interactions with adult human nAChR.

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药物靶点

药物	目标	类	生物	药理作用	行动
Doxacurium	神经乙酰胆碱受体亚基α2	蛋白质	人类	是的	拮抗剂	细节
Metocurine	神经乙酰胆碱受体亚基α2	蛋白质	人类	是的	拮抗剂	细节
Metocurine碘化	神经乙酰胆碱受体亚基α2	蛋白质	人类	是的	拮抗剂	细节
Rocuronium	神经乙酰胆碱受体亚基α2	蛋白质	人类	是的	拮抗剂	细节
筒箭毒碱	神经乙酰胆碱受体亚基α2	蛋白质	人类	是的	拮抗剂	细节
维库	神经乙酰胆碱受体亚基α2	蛋白质	人类	是的	拮抗剂	细节