Sells D M, Gibson J P
Merrell Dow Research Institute, Merrell Dow Pharmaceuticals, Cincinnati, Ohio 45215.
Toxicol Pathol. 1987;15(4):457-67. doi: 10.1177/019262338701500411.
The carcinogenic potential of medroxalol hydrochloride, an antihypertensive agent with beta 1 adrenergic cardiac blocking properties, and beta 2 and some alpha 1 vasodilating activity, was studied by dietary administration. Long Evans rats were treated for 2 years and CD-1 mice for 18 months at dosages of 0, 50, 250 or 500 mg/kg/day. Medroxalol did not produce any evidence of a tumorigenic effect in the Long Evans rat, but graying of pigmented hair was noted at 250 and 500 mg/kg/day and is probably related to melanin binding of the drug. In the CD-1 mouse, there was a dose related increase in uterine leiomyomas that was statistically significant (p less than 0.05) at doses of 250 and 500 mg/kg/day. The incidence at 50 mg/kg/day was not different from control. Endometrial stromal sarcomas were observed only in treated mice, and pairwise comparison with controls indicated a statistically significant difference (p less than 0.05) only at the lowest dosage (50 mg/kg/day). The latter finding may not be related to treatment since there was no dose response and the incidence in the two higher dose groups was neither statistically significant nor higher than occasionally seen in other control groups.
通过饮食给药研究了盐酸美多心安的致癌潜力。盐酸美多心安是一种具有β1肾上腺素能心脏阻滞特性以及β2和部分α1血管舒张活性的抗高血压药物。对Long Evans大鼠进行了2年的治疗，对CD - 1小鼠进行了18个月的治疗，剂量分别为0、50、250或500毫克/千克/天。在Long Evans大鼠中，美多心安未产生任何致癌作用的证据，但在250和500毫克/千克/天剂量下观察到有色毛发变灰，这可能与药物的黑色素结合有关。在CD - 1小鼠中，子宫平滑肌瘤呈剂量相关增加，在250和500毫克/千克/天剂量下具有统计学意义（p小于0.05）。50毫克/千克/天剂量下的发病率与对照组无差异。仅在治疗小鼠中观察到子宫内膜间质肉瘤，与对照组的成对比较表明，仅在最低剂量（50毫克/千克/天）时有统计学意义（p小于0.05）。后一发现可能与治疗无关，因为没有剂量反应，且两个较高剂量组的发病率既无统计学意义也不高于其他对照组偶尔出现的发病率。
