Naguib Mohamed, Brull Sorin J
Department of Anesthesiology and Pain Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Curr Opin Anaesthesiol. 2009 Aug;22(4):483-90. doi: 10.1097/ACO.0b013e32832b8cff.
We review the efficacy and safety of gantacurium and AV002, two novel, investigational fumarate-based nondepolarizing neuromuscular blockers, as well as sugammadex and cysteine, two novel reversal drugs that have no acetylcholinesterase inhibition properties.
Gantacurium (with a pharmacodynamic profile similar to that of succinylcholine) and AV002 (with an intermediate duration of action) have shown efficacy in animals and, for gantacurium, in humans. Animal data have shown that exogenous administration of the amino acid cysteine accelerates the natural chemical degradation of both gantacurium and AV002 via the cysteine adduction pathway. Another reversal drug, sugammadex (a modified gamma-cyclodextrin and the first selective relaxant binding agent), forms very tight complexes in a 1: 1 ratio with steroidal neuromuscular blocking agents.
In a multicenter phase-2 randomized controlled study in the European Union, the efficacy and safety of gantacurium were evaluated, but results have not yet been published. Sugammadex is currently available in the European Union, but the United States Food and Drug Administration has had concerns about its safety (hypersensitivity and allergic reactions) and has asked for additional safety data. It is hoped that the widespread use of sugammadex in the European Union will provide additional information.
我们综述了甘氨酰环素和AV002这两种新型的、基于富马酸盐的非去极化神经肌肉阻滞剂以及舒更葡糖钠和半胱氨酸这两种无乙酰胆碱酯酶抑制特性的新型逆转药物的疗效和安全性。
甘氨酰环素（药效学特征与琥珀酰胆碱相似）和AV002（作用持续时间中等）在动物实验中已显示出疗效，甘氨酰环素在人体实验中也有疗效。动物实验数据表明，外源性给予氨基酸半胱氨酸可通过半胱氨酸加成途径加速甘氨酰环素和AV002的自然化学降解。另一种逆转药物舒更葡糖钠（一种改性γ-环糊精，也是首个选择性肌松药结合剂）能与甾体类神经肌肉阻滞剂以1:1的比例形成非常紧密的复合物。
在欧盟进行的一项多中心2期随机对照研究中，对甘氨酰环素的疗效和安全性进行了评估，但结果尚未发表。舒更葡糖钠目前在欧盟已上市，但美国食品药品监督管理局对其安全性（超敏反应和过敏反应）存在担忧，并要求提供更多安全性数据。希望舒更葡糖钠在欧盟的广泛使用能提供更多信息。
