Effect of 2 anti-arrhythmic drugs aprindine and moxaprindine on the replication capacity of murine and human haemopoietic cells.
Aprindine, a potent anti-arrhythmic agent, occasionally seems responsible for agranulocytosis. In order to study its potential haematological toxicity, 3 different in vitro tests were used: (a) the capacity of human and mice bone marrow to incorporate tritiated thymidine (3HTdR), (b) the capacity of stimulated human blood lymphocytes to incorporate 3HTdR and (c) the capacity of human granulocyte-macrophage stem cells to form colonies in agar. For all these tests aprindine was found to be toxic at concentrations close to the clinical therapeutic serum concentration. Moxaprindine, chemically very close to aprindine exhibits also an anti-arrhythmic activity. It was examined in the same tests in parallel with the study af aprindine. Moxaprindine also exhibited haematological toxicity in the tests but at a significantly higher concentration, approximately twice that of aprindine. Assuming that these in vitro tests are relevant to the in vivo haematological toxicity, moxaprindine could be considered a clinically safer anti-arrhythmic agent than aprindine.
D000818:Animals; D001073:Aprindine / Q000031:analogs & derivatives / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007192:Indenes / Q000633:toxicity*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D013936:Thymidine / Q000378:metabolism
D007192:Indenes; C023489:moxaprindine; D001073:Aprindine; D013936:Thymidine