Nigrovic V, Auen M, Wajskol A
Anesthesiology. 1985 May;62(5):606-9. doi: 10.1097/00000542-198505000-00011.
Inactivation of atracurium in vivo has been postulated to proceed along two pathways: Hofmann elimination and ester hydrolysis. Since an end product of Hofmann elimination (acrylate) may be potentially toxic, the authors conducted a study to determine the extent of degradation via enzyme-catalyzed hydrolysis relative to that via Hofmann elimination. The enzyme carboxylesterase was inhibited by the pretreatment of rats with an organophosphorous compound, triorthotolyl phosphate (TOTP). Skeletal muscle relaxation produced either by d-tubocurarine or succinylcholine was not influenced by the pretreatment. This indicates that TOTP does not alter directly the paralyzing properties of either depolarizing or nondepolarizing muscle relaxants. Relaxation produced by atracurium, however, was prolonged markedly and the rate of recovery from relaxation was decreased. The authors conclude: 1) enzyme-catalyzed hydrolysis is probably responsible for the short duration of action of atracurium; 2) Hofmann elimination, at least in rats, probably is not the principal degradation pathway; and 3) the opportunity for in vivo generation of large amounts of potentially toxic end products is less than previously implied.
霍夫曼消除和酯水解。由于霍夫曼消除的终产物（丙烯酸酯）可能具有潜在毒性，作者进行了一项研究，以确定相对于霍夫曼消除，酶催化水解的降解程度。通过用有机磷化合物磷酸三邻甲苯酯（TOTP）预处理大鼠来抑制酶羧酸酯酶。由右旋筒箭毒碱或琥珀酰胆碱产生的骨骼肌松弛不受预处理的影响。这表明TOTP不会直接改变去极化或非去极化肌肉松弛剂的麻痹特性。然而，阿曲库铵产生的松弛明显延长，且从松弛状态恢复的速率降低。作者得出结论：1）酶催化水解可能是阿曲库铵作用持续时间短的原因；2）至少在大鼠中，霍夫曼消除可能不是主要的降解途径；3）体内产生大量潜在有毒终产物的可能性比以前认为的要小。
