Hua J, Olsson A, Sheng Y, Pero R W
Department of Molecular Ecogenetics, Wallenberg Laboratory, University of Lund, Sweden.
Anticancer Drugs. 1995 Jun;6(3):451-5. doi: 10.1097/00001813-199506000-00014.
A neutralized formulation (Neu-Sensamide) of metoclopramide (MCA) has been shown to possess reduced sedative side effects compared with the conventional acidic formulations (Primperan). The acidic formulation of MCA has also been shown to sensitize the effect of ionizing radiation (6-8 Gy) using human squamous cell carcinomas from the head and neck xenografted to nude mice. In the present study, 2 mg MCA/kg body weight 1-3 h before treatment with 1 Gy radiation (single dose) was evaluated in scid mice xenografted with a human lung adenocarcinoma. MCA given alone in acidic or neutralized formulations did not show any effect on tumor growth retardation. However, when combined with radiation, both acidic and neutralized formulations of MCA sensitized the cytotoxic effect of radiation directed against the tumors by increasing tumor doubling time, tumor quadrupling time and specific growth delay, and by decreasing area under growth curve measurements. In addition, there was no statistically significant difference between the two formulations of MCA in the efficacy of sensitizing the cytotoxicity of a single low dose (1 Gy) of radiation.
与传统酸性制剂（胃复安）相比，胃复安（MCA）的一种中和制剂（Neu - Sensamide）已显示出镇静副作用有所减少。胃复安的酸性制剂还被证明可使移植到裸鼠的人头部和颈部鳞状细胞癌对电离辐射（6 - 8 Gy）的作用敏感。在本研究中，在用1 Gy辐射（单次剂量）治疗前1 - 3小时，对移植有人肺腺癌的重度联合免疫缺陷（scid）小鼠评估了2 mg MCA/千克体重的剂量。单独给予酸性或中和制剂形式的胃复安对肿瘤生长抑制均无任何作用。然而，当与辐射联合使用时，胃复安的酸性和中和制剂均通过增加肿瘤倍增时间、肿瘤四倍时间和特定生长延迟，并通过减少生长曲线下面积测量值，使针对肿瘤的辐射细胞毒性作用敏感化。此外，在使单次低剂量（1 Gy）辐射的细胞毒性敏感化的功效方面，胃复安的两种制剂之间没有统计学上的显著差异。
