Selective inhibitory effects of chlorpromazine and imipramine on platelet aggregation

The effects of chlorpromazine (CPZ) and imipramine (IMP) on platelet aggregation in vitro were investigated. Both CPZ and IMP inhibited epinephrine-induced secondary aggregation in a dose-dependent fashion and changed adenosine diphosphate (ADP)-induced irreversible aggregation into a reversible response in human platelets. With rabbit platelets, CPZ (0.6-20 microM) and IMP (6-60 microM) showed a selective inhibitory effect on the aggregation by collagen, whereas, even at 200 microM, this effect was found neither in arachidonic acid (AA)-induced aggregation nor in ADP-induced one. CPZ and IMP also inhibited human platelet aggregations induced by collagen, but not by AA. The antiaggregating action of CPZ and IMP was thought to be due to their inhibitory effects on AA liberation from platelet membranes, suggesting that they might inhibit participating enzymes (phospholipase A2, C or lipase) or the process of the activation of the enzymes.