的力量bupivacaine立体异构体检测体外和体内:生物化学,电生理和神经行为的研究。

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Vladimirov M, nautica C Mok WM Strichartz G

的力量bupivacaine立体异构体检测体外和体内:生物化学,电生理和神经行为的研究。

麻醉学。2000年9月,93 (3):744 - 55。

PubMed ID

10969308 (在PubMed

]

文摘

背景:手性局部麻醉剂,如ropivacaine levobupivacaine,有潜力优势外消旋混合物显示减少有毒副作用。然而,这些S -异构体(左旋的,或“-”)据说也有效力低于他们的光学对映体,可能导致在治疗指数没有优势。力量为当地麻醉剂抑制Na +渠道或动作电位取决于膜电位的模式,所以也stereopotency比例。这里作者有量化的stereopotencies R - S -,和外消旋bupivacaine,比较几种神经元的体外测定Na +渠道与体内功能性神经阻滞,建立相对的效能和更好地理解不同的渠道模式的作用抑制整体功能的麻醉。方法:结合bupivacaine Na +渠道评估间接的拮抗作用[3 h] -batrachotoxin绑定到老鼠的大脑突触体。抑制Na +电流直接通过bupivacaine化验voltage-clamped GH-3神经内分泌细胞。神经行为功能受到bupivacaine经皮注射(0.1毫升;0.0625 -1.0%)在大鼠坐骨神经和半定量的化验。浓度的R - S -,和外消旋bupivacaine比较大小和持续时间的行动。结果:竞争batrachotoxin位移有stereopotency比R: S = 3:1。 Inhibition of Na+ currents with different prepulse potentials shows that S > R potency when the membrane is hyperpolarized, and R > S potency when it is depolarized from normal resting values. Functional deficits assayed in vivo usually demonstrate no consistent enantioselectivity and only a modest stereopotency (R:S = 1.2-1.3) for peak analgesia achieved at the lowest doses. Other functions display no significant stereopotency in either the degree, the duration, or their product (area under the curve) at any dose. CONCLUSION: Although the in vitro actions of bupivacaine showed stereoselectivity ratios of 1.3-3:1 (R:S), in vivo nerve block at clinically used concentrations showed much smaller ratios for peak effect and no significant enantioselectivity for duration. A primary role for the blockade of resting rather than open or inactivated Na+ channels may explain the modest stereoselectivity in vivo, although stereoselective factors controlling local disposition cannot be ruled out. Levo-(S-)bupivacaine is effectively equipotent to R- or racemic bupivacaine in vivo for rat sciatic nerve block.

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药物靶点

药物	目标	类	生物	药理作用	行动
Levobupivacaine	钠离子通道蛋白类型10亚基α	蛋白质	人类	是的	抑制剂	细节