Cytotoxic effects of imipramine on platelets

Incubation for 30 min at 30° with 1 mM imipramine, chlorpromazine or phencyclidine produced increases in creatine phosphokinase (CPK) activity of rat platelet-rich plasma (PRP). Increases in lactic dehydrogenase (LDH) activity of human PRP were produced by imipramine at 0.5 mM. Ouabain, diphenylhydantoin, calcium chloride, EDTA and thrombin did not affect CPK activity of rat PRP. None of the dugs tested except 10 mM diphenylhydantoin affected CPK or LDH activity in platelet-poor plasma. Increases in enzyme activity of PRP produced by 1 mM imipramine were associated with a decrease in platelet count. The increases were independent of temperature of incubation from 0° to 30° and were maximal after a 5-min incubation. The release of LDH and CPK caused by the above drugs is not related to platelet aggregation or the platelet release reaction. The increases in LDH and CPK activity in PRP appear to be the result of platelet destruction or damage to the platelet plasma membrane with release of these enzymes.