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 hum an brain astrocytoma (T24) when given intramuscularly to mice every th ird dap for 14-20 days. 3-CPA was shown to have the same efficacy on t umor growth inhibition as neutral metoclopramide (neutral MCA) at the doses of 10-40 mg/kg when evaluated by tumor doubling time: tumor grow th time for tumor volumes to reach 1000 mm and area under growth curve . 3-CPA ar the dose of 3 x 40 mg/kg was also shown to enhance the cyto toxicity induced by a single dose of cisplatin at 7.5 mg/kg. A dose of less than or equal to 160 mg:kg of 3-CPA did not show any notable ext rapyramidal symptoms which was observed fcr neutral MCA treated mice a t the dose of 20 mg/kg. The lethal response dose of 3-CPA for scid mic e was 320 mg/kg which is 4 rimes higher than that determined for neutr al MCA (80 mg/kg). These results support 3-CPA as a good candidate dru g representing a new generation of benzamides for further clinical dev elopment as a cancer therapy drug.