The toxicity of amodiaquine and its principal metabolites towards mononuclear leucocytes and granulocyte/monocyte colony forming units.

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Abstract
The cytotoxicity of amodiaquine (AQ), amodiaquine quinoneimine (AQQI) and desethylamodiaquine (AQm) has been assessed in comparison with that of chloroquine (CQ) using mononuclear leucocytes (MNL) and granulocyte/monocyte colony forming units (GM-CFU) from haematologically normal subjects. Toxicity toward MNL was assessed after 2 h and 16 h incubations with each compound. After 2 h, AQ, AQm and AQQI but not CQ (within the concentration range 1-100 mumols l-1) produced a significant decrease in cell viability. After 16 h, all four compounds significantly increased cell death. After both 2 h and 16 h incubations CQ was the least toxic and AQQI the most toxic of the four compounds towards MNL. Toxicity to GM-CFU was assessed by the inhibition of colony formation in vitro. After 10-14 days incubation, there was significant concentration-dependent inhibition of colony formation by AQ, AQm, AQQI and CQ (within the range 0.1-10.0 mumols l- 1). There were no significant differences between the ability of the four compounds to inhibit colony formation but toxicity towards GM-CFU was observed at drug concentrations at least 10-fold lower than those that were toxic to MNL. These data show that the four compounds are equally toxic in vitro toward GM-CFU, although some differences in their toxicity toward MNL were seen. The possible mechanisms of AQ's toxicity are discussed.