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蒽环类抗生素阿霉素是治疗多种实体瘤的有效药物。然而,它的临床应用一直被各种与剂量相关的心脏毒性反应所限制,当超过最大的累积剂量550mg/m~2时,这种毒性反应出现的频率大幅度上升。心脏毒性的机理迄今未能解释。作者最近发现,阿霉素体外对大鼠及人心脏的鸟苷酸环化酶活性,具有选择性抑制作用。另外的实验指出,类似的抑制作用在大鼠体内注射一次之后,可能持续24小时。对比之下,当结构相关的类似物——阿克拉霉素以同一体系进行试验时,则未见对鸟苷酸环化酶的抑制作用。既然阿克拉霉素比阿
Anthracycline Adriamycin is an effective drug for the treatment of many solid tumors. However, its clinical utility has been limited by a variety of dose-related cardiotoxic reactions, and the frequency of this toxic reaction has increased significantly beyond the maximum cumulative dose of 550 mg / m 2. The mechanism of cardiotoxicity has so far failed to explain. The authors recently found that doxorubicin has a selective inhibitory effect on guanylate cyclase activity in rats and human hearts in vitro. Additional experiments indicate that similar inhibition may last up to 24 hours after one injection in rats. In contrast, no guanylate cyclase inhibition was observed when the structurally related analogue acyclovir was tested in the same system. Since aclacinomycin than a