Neutral metoclopramide sensitizes cytotoxicity induced by ionizing radiation in SCID mice xenografted with a human brain astrocytoma.
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.
Hua
J
J
Department of Cell and Molecular Biology, University of Lund, Sweden. Jianyi.Hua@wblab.lu.se
Olsson
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D000818:Animals; D001254:Astrocytoma / Q000188:drug therapy / Q000532:radiotherapy*; D001812:Blood-Brain Barrier; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003131:Combined Modality Therapy; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D011838:Radiation-Sensitizing Agents; D008787:Metoclopramide