Toxic effects of the histamine H(2) receptor antagonist metiamide on bone-marrow haemopoietic and stromal progenitor cells in vitro.

The histamine H(2)-receptor antagonist, metiamide has been shown to cause agranulocytosis in vivo. In vitro colony forming assays for bone-marrow stromal fibroblast progenitors (CFU-F) and granulocyte/macrophage progenitor cells (CFU-GM) were performed, using murine bone marrow, to assess the relative sensitivity of committed haemopoietic cells, and the marrow stromal microenvironment to metiamide toxicity. CFU-F were more susceptible than CFU-GM to inhibition by metiamide, with 50% inhibition of colony formation (ID(50)) at 17 and 180 mug/ml in the CFU-F and CFU-GM assays, respectively. Inhibition of CFU-GM required the continuous presence of the drug, while CFU-F were inhibited similarly by either short-term (20-hr) or prolonged (10-day) incubation with metiamide (ID(50) 27 and 17 mug/ml, respectively). It is suggested that bone-marrow stromal cell damage may be an important contributory factor in the haemopoietic toxicity of metiamide.