Yoshida M, Fujioka A, Nakano K, Yuasa C, Toko T, Takeda S, Unemi N
Anticancer and Antimicrobials Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Anticancer Res. 1996 Sep-Oct;16(5A):2875-9.
Menogaril is an antitumor agent different from other anthracyclines in that it is active after oral administration; therefore, extravasation is not a side effect. In this basic study, we examined the antitumor activity of menogaril against malignant lymphoma. We compared its activity towards experimental malignant lymphoma with that of Adriamycin, epirubicin, pirarubicin, vincristine, and etoposide, treating mice with each drug at the dose schedule usually used for patients. Menogaril rapidly penetrated lymphoma cells and remained there at least 3 hours after the drug was washed out. Menogaril cleaved more double-stranded DNA in lymphoma cells than Adriamycin, epirubicin, pirarubicin, or etoposide. Menogaril had stronger antitumor activity against experimental malignant lymphoma in mice than Adriamycin, epirubicin, vincristine, and etoposide. Menogaril significantly lengthened the life span of mice bearing one of three lymphoma cell lines resistant to cisplatin, vincristine, or cyclophosphamide. Menogaril had stronger antitumor activity against the human malignant lymphoma xenograft LM-3 than Adriamycin. The strength of the cytotoxic activity of Menogaril might arise from its ready penetration into cells and its cleavage of double-stranded DNA. Therefore, Menogaril might become a useful drug for the treatment of patients with malignant lymphoma by oral administration; 7 days of administration was effective in the in vivo experiments.
美诺加明是一种不同于其他蒽环类药物的抗肿瘤药物，其口服后具有活性；因此，外渗不是副作用。在这项基础研究中，我们研究了美诺加明对恶性淋巴瘤的抗肿瘤活性。我们将其对实验性恶性淋巴瘤的活性与阿霉素、表柔比星、吡柔比星、长春新碱和依托泊苷进行了比较，按照通常用于患者的剂量方案用每种药物治疗小鼠。美诺加明能迅速穿透淋巴瘤细胞，在药物被洗脱后至少在细胞内停留3小时。美诺加明在淋巴瘤细胞中切割的双链DNA比阿霉素、表柔比星、吡柔比星或依托泊苷更多。美诺加明对小鼠实验性恶性淋巴瘤的抗肿瘤活性比阿霉素、表柔比星、长春新碱和依托泊苷更强。美诺加明显著延长了携带对顺铂、长春新碱或环磷酰胺耐药的三种淋巴瘤细胞系之一的小鼠的寿命。美诺加明对人恶性淋巴瘤异种移植瘤LM-3的抗肿瘤活性比阿霉素更强。美诺加明细胞毒性活性的强度可能源于其易于穿透细胞以及对双链DNA的切割。因此，美诺加明可能成为一种通过口服给药治疗恶性淋巴瘤患者的有用药物；在体内实验中，给药7天是有效的。
