A New Agent to Reverse the Effects of Benzylisoquinoline and Steroidal Neuromuscular-blocking Agents
A New Agent to Reverse the Effects of Benzylisoquinoline and Steroidal Neuromuscular-blocking Agents
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DOI：
10.1097/aln.0b013e3182910213
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发表时间：
2013-08-01
期刊：
影响因子：
8.8
通讯作者：
Eikermann, Matthias
中科院分区：
文献类型：
--
作者：
Hoffmann, Ulrike;Grosse-Sundrup, Martina;Eikermann, Matthias
简介：为了评估calabadion 1，葫芦[n]脲家族的分子容器的无环成员，是否逆转benzylisoquinoline和甾体神经肌肉阻滞剂effects.Methods：总共60只大鼠麻醉，气管切开，和仪器与IV和动脉导管。给予罗库溴铵（3.5 mg/kg）或顺铂（0.6 mg/kg），并通过加速度肌描记术定量神经肌肉传递。以30、60和90 mg/kg（罗库溴铵）或90、120和150 mg/kg（顺库溴铵）的Calabadion 1或0.06/0.012 mg/ kg的新斯的明/格隆溴铵在最大抽搐抑制下给药，并使用（1）H NMR测定法测定肾脏Calabadion 1消除。作者还测量了心率、动脉血气参数和动脉血压。罗库溴铵给药后，自主呼吸的恢复和四个成串比率恢复至0.9的时间从安慰剂组的12.3 +/- 1.1和16.2 +/- 3.3分钟加速至新斯的明/格隆溴铵组的4.6 +/- 1.8分钟至15 +/-Calabadion 1（90 mg/kg）分别为8和84 +/- 33 s。在给予顺利库铵后，呼吸恢复和四个训练的比率从安慰剂组的8.7 +/- 2.8和9.9 +/- 1.7分钟加速到新斯的明/格隆溴铵组的2.8 +/- 0.8和7.6 +/- 2.1分钟，再到calabadion 1组的47 +/- 13和87 +/- 16秒（150 mg/kg）。Calabadion 1不影响心率、平均动脉血压、pH值、二氧化碳分压和氧分压。超过90%的IV给药的Calabadion 1出现在1小时内的尿液中。结论：Calabadion 1是一种快速和完全逆转的类固醇和苄基异喹啉神经肌肉阻滞剂的作用的新药。
Introduction: To evaluate whether calabadion 1, an acyclic member of the Cucurbit[n] uril family of molecular containers, reverses benzylisoquinoline and steroidal neuromuscular- blocking agent effects.Methods: A total of 60 rats were anesthetized, tracheotomized, and instrumented with IV and arterial catheters. Rocuronium (3.5 mg/kg) or cisatracurium (0.6 mg/kg) was administered and neuromuscular transmission quantified by acceleromyography. Calabadion 1 at 30, 60, and 90 mg/kg (for rocuronium) or 90, 120, and 150 mg/kg (for cisatracurium), or neostigmine/glycopyrrolate at 0.06/0.012 mg/ kg were administered at maximum twitch depression, and renal calabadion 1 elimination was determined by using a(1)H NMR assay. The authors also measured heart rate, arterial blood gas parameters, and arterial blood pressure.Results: After the administration of rocuronium, resumption of spontaneous breathing and recovery of train-of-four ratio to 0.9 were accelerated from 12.3 +/- 1.1 and 16.2 +/- 3.3 min with placebo to 4.6 +/- 1.8 min with neostigmine/glycopyrrolate to 15 +/- 8 and 84 +/- 33 s with calabadion 1 (90 mg/kg), respectively. After the administration of cisatracurium, recovery of breathing and train-of-four ratio of 0.9 were accelerated from 8.7 +/- 2.8 and 9.9 +/- 1.7 min with placebo to 2.8 +/- 0.8 and 7.6 +/- 2.1 min with neostigmine/glycopyrrolate to 47 +/- 13 and 87 +/- 16 s with calabadion 1 (150 mg/kg), respectively. Calabadion 1 did not affect heart rate, mean arterial blood pressure, pH, carbon dioxide pressure, and oxygen tension. More than 90% of the IV administered calabadion 1 appeared in the urine within 1 h.Conclusion: Calabadion 1 is a new drug for rapid and complete reversal of the effects of steroidal and benzylisoquinoline neuromuscular-blocking agents.