Dreisin R B, Mostow S R
J Lab Clin Med. 1979 Apr;93(4):674-8.
Although N-acetyl-L-cysteine (Mucomyst) is an effective mycolytic, numerous investigations have failed to demonstrate a consistent improvement in pulmonary mechanics following its use. In order to determine whether its beneficial mucolytic activity might be counterbalanced by a deleterious direct effect on cilia, we studied its effect on the activity of ciliated epithelium in the ferret tracheal organ culture system. N-acetyl-L-cysteine consistently caused progressive time-dependent ciliostasis at concentrations clinically employed, with complete ciliary paralysis within 8 hr. The effect was only partially reversed by the removal of the drug. Control preparations retained full ciliary activity for 3 to 12 weeks. In order to determine the active site on the N-acetyl-L-cysteine molecule, we investigated the ciliostatic effects of five of its chemical analogs. Isomolar N-acetyl-L-alanine was not ciliostatic, indicating the necessity of a sulfhydryl group for activity. Ciliostasis was independent of isomeric structure, acetylation, and chain length, as evidenced by the similar ciliostatic effects of L-cysteine, D-cysteine, 2-mercaptoethylamine, and N-acetyl-L-homocysteine. We conclude that N-acetyl-L-cysteine induces partially reversible ciliostasis of tracheal epithelium via its sulfhydryl group; prolonged use of this drug may impair mucociliary clearance.
尽管N-乙酰-L-半胱氨酸（沐舒坦）是一种有效的黏液溶解剂，但大量研究未能证明使用该药物后肺力学有持续改善。为了确定其有益的黏液溶解活性是否可能被对纤毛的有害直接作用所抵消，我们在雪貂气管器官培养系统中研究了它对纤毛上皮活性的影响。N-乙酰-L-半胱氨酸在临床使用浓度下持续导致时间依赖性的渐进性纤毛运动停滞，8小时内完全出现纤毛麻痹。去除药物后，这种作用仅部分逆转。对照制剂在3至12周内保持完全的纤毛活性。为了确定N-乙酰-L-半胱氨酸分子上的活性位点，我们研究了其五种化学类似物的纤毛运动抑制作用。等摩尔的N-乙酰-L-丙氨酸没有抑制纤毛运动，表明活性需要巯基。L-半胱氨酸、D-半胱氨酸、2-巯基乙胺和N-乙酰-L-高半胱氨酸具有相似的纤毛运动抑制作用，这证明纤毛运动停滞与异构体结构、乙酰化和链长无关。我们得出结论，N-乙酰-L-半胱氨酸通过其巯基诱导气管上皮细胞出现部分可逆的纤毛运动停滞；长期使用该药物可能会损害黏液纤毛清除功能。
