Toxicity, antitumor and chemosensitizing effects of 3-chloroprocainamide.
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.
Hua
J
J
Department of Cell and Molecular Biology, University of Lund, Sweden.
Pero
R W
RW
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001254:Astrocytoma / Q000188:drug therapy*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011342:Procainamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; C072799:declopramide; D011342:Procainamide; D008787:Metoclopramide; D002945:Cisplatin