Nigrovic V, Smith S
Br J Anaesth. 1987 May;59(5):617-21. doi: 10.1093/bja/59.5.617.
Atracurium was incubated in 0.9% sodium chloride solution at pH 7.4 and 37 degrees C. The following compounds were added to the incubation solution: propionic acid, alanine and cysteine (0.1 mol litre-1 final concentration). Metocurine was also incubated with cysteine under identical conditions. Aliquots of the incubation solutions were injected i.v. to anaesthetized rats at the start (0 min) and at the end of incubation (45 min), and the indirectly elicited, single twitches of the gastrocnemius muscle were observed. Whereas inactivation of atracurium proceeded slowly in the control solution and in the presence of sodium propionate, the presence of alanine and, especially, of cysteine markedly enhanced the inactivation. Incubation of metocurine with cysteine did not alter the pharmacological responses. The concentration of cysteine decreased progressively during its incubation with atracurium (37 degrees C, pH 7.4). We conclude that the data are compatible with the postulate that a nucleophile may enhance the degradation of atracurium by a reaction with the parent compound (nucleophilic substitution reaction), by reaction with acrylates (Michael addition) or both.
将阿曲库铵在pH 7.4、37℃的0.9%氯化钠溶液中孵育。向孵育溶液中加入以下化合物：丙酸、丙氨酸和半胱氨酸（终浓度为0.1 mol/L）。美托库铵也在相同条件下与半胱氨酸一起孵育。在孵育开始时（0分钟）和孵育结束时（45分钟），将等分的孵育溶液静脉注射给麻醉大鼠，并观察腓肠肌间接诱发的单次抽搐。在对照溶液中和存在丙酸钠的情况下，阿曲库铵的失活进行缓慢，而丙氨酸尤其是半胱氨酸的存在显著增强了失活。美托库铵与半胱氨酸孵育并未改变药理反应。半胱氨酸与阿曲库铵孵育期间（37℃，pH 7.4）其浓度逐渐降低。我们得出结论，这些数据与以下假设相符：亲核试剂可能通过与母体化合物反应（亲核取代反应）、与丙烯酸酯反应（迈克尔加成）或两者兼而有之来增强阿曲库铵的降解。
