Platelet-Activating Factor-Induced Aggregation of Human Platelets Specifically Inhibited by Triazolobenzodiazepines

Abstract

Platelet-activating factor (PAF), a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation. The mechanisms by which PAF acts are largely unknown, partly because of the lack of specific inhibitors for PAF-elicited responses. It was found that in washed human platelets the psychotropic triazolobenzodiazepine drugs alprazolam and triazolam potently inhibited PAF-induced changes in shape, aggregation, and secretion. The effects were specific for PAF activation, since the responses of human platelets to adenosine diphosphate, thrombin, epinephrine, collagen, arachidonate, and the calcium ionophore A23187 were not inhibited by the triazolobenzodiazepines. These psychotropic drugs should be useful in investigating the possibility that PAF or PAF-like phospholipids play a role in neuronal function and in elucidating biochemical mechanisms activated specifically by PAF in a variety of cells.