Hua J, Olsson A R, Pero R W
Department of Cell and Molecular Biology, University of Lund, Sweden.
Int J Cancer. 1997 Dec 10;73(6):871-4. doi: 10.1002/(sici)1097-0215(19971210)73:6<871::aid-ijc18>3.0.co;2-7.
A formulation of metoclopramide (MCA) conformationally altered by neutralization of pH (nMCA, Neu-Sensamide) has been shown to have the same efficacy of enhancing the cytotoxicity of a single dose of 1 Gy radiation as acidic formulations (e.g., Primperan, Sensamide) in a human lung adenocarcinoma (H2981) xenografted into SCID mice. In the present study, 2 x 1 Gy radiation was combined with 2 x 2 mg nMCA/kg body weight injected 2 hr before radiation treatment for evaluation of radiosensitization in SCID mice xenografted with a human brain astrocytoma (T24). Given in this treatment schedule, nMCA alone at 2 mg/kg showed no cytotoxic effect on tumor growth in vivo. When combined with 2 x 1 Gy of radiation, however, the cytotoxicity was significantly increased as measured by tumor growth delay over the radiation-only-treated group. Furthermore, nMCA was absorbed into brains of mice and rats as efficiently as acidic MCA (aMCA) when analyzed 45 min after i.m. injection by high-performance liquid chromatography.
通过调节pH值使甲氧氯普胺（MCA）构象发生改变的制剂（nMCA，Neu - Sensamide）已被证明，在移植到SCID小鼠体内的人肺腺癌（H2981）中，其增强单剂量1 Gy辐射细胞毒性的效果与酸性制剂（如胃复安、Sensamide）相同。在本研究中，将2×1 Gy辐射与在放疗前2小时注射的2×2 mg nMCA/kg体重相结合，以评估移植了人脑星形细胞瘤（T24）的SCID小鼠的放射增敏作用。按照此治疗方案给药，单独使用2 mg/kg的nMCA对体内肿瘤生长没有细胞毒性作用。然而，当与2×1 Gy辐射联合使用时，通过肿瘤生长延迟来衡量，其细胞毒性比仅接受辐射治疗的组显著增加。此外，在肌肉注射45分钟后通过高效液相色谱分析发现，nMCA与酸性MCA（aMCA）一样有效地被吸收到小鼠和大鼠的大脑中。
