Hua J, Pero R W
Department of Cell and Molecular Biology, University of Lund, Sweden.
Acta Oncol. 1997;36(8):811-6. doi: 10.3109/02841869709001362.
3-Chloroprocainamide (3-CPA), an analog of metoclopramide (MCA), dose-dependently inhibited tumor growth in scid mice xenografted with a human brain astrocytoma (T24) when given intramuscularly to mice every third day for 14-20 days. 3-CPA was shown to have the same efficacy on tumor growth inhibition as neutral metoclopramide (neutral MCA) at the doses of 10-40 mg/kg when evaluated by tumor doubling time, tumor growth time for tumor volumes to reach 1000 mm3 and area under growth curve. 3-CPA at the dose of 3 x 40 mg/kg was also shown to enhance the cytotoxicity induced by a single dose of cisplatin at 7.5 mg/kg. A dose of < or = 160 mg/kg of 3-CPA did not show any notable extrapyramidal symptoms which was observed for neutral MCA treated mice at the dose of 20 mg/kg. The lethal response dose of 3-CPA for scid mice was 320 mg/kg which is 4 times higher than that determined for neutral MCA (80 mg/kg). These results support 3-CPA as a good candidate drug representing a new generation of benzamides for further clinical development as a cancer therapy drug.
3-氯普鲁卡因酰胺（3-CPA）是甲氧氯普胺（MCA）的类似物，当每隔一天给接种人脑星形细胞瘤（T24）的重症联合免疫缺陷（scid）小鼠肌肉注射14 - 20天时，它能剂量依赖性地抑制肿瘤生长。通过肿瘤倍增时间、肿瘤体积达到1000立方毫米的肿瘤生长时间以及生长曲线下面积评估，在10 - 40毫克/千克的剂量下，3-CPA对肿瘤生长抑制的效果与中性甲氧氯普胺（中性MCA）相同。3-CPA以3×40毫克/千克的剂量给药时，还能增强7.5毫克/千克单剂量顺铂诱导的细胞毒性。剂量≤160毫克/千克的3-CPA未显示出任何明显的锥体外系症状，而在20毫克/千克剂量下接受中性MCA治疗的小鼠则出现了这种症状。scid小鼠对3-CPA的致死反应剂量为320毫克/千克，这比中性MCA（80毫克/千克）的致死反应剂量高4倍。这些结果支持3-CPA作为一种优秀的候选药物，代表新一代苯甲酰胺类药物，可进一步作为癌症治疗药物进行临床开发。
