Toxicity, antitumor and chemosensitizing effects of 3-chloroprocainamide.

Abstract

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.

• Authors: J Hua, R W Pero
• Journal: Acta oncologica (Stockholm, Sweden) (Acta Oncol) Vol. 36 Issue 8 Pg. 811-6 ( 1997) ISSN: 0284-186X [Print] England
• PMID: 9482687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• declopramide
• Procainamide
• Metoclopramide
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Astrocytoma (drug therapy)
• Brain Neoplasms (drug therapy)
• Cisplatin (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Drug Screening Assays, Antitumor
• Female
• Humans
• Male
• Metoclopramide (pharmacology, toxicity)
• Mice
• Mice, SCID
• Neoplasm Transplantation
• Procainamide (analogs & derivatives, pharmacology, toxicity)
• Transplantation, Heterologous