CV3988 inhibits in vivo platelet aggregation induced by PAF-acether and collagen

Platelet activating factor (PAF-acether) was shown to cause a fall in the circulating platelet count and blood pressure (BP) in anaesthetised rabbits. CV3988 caused a dose-dependent inhibition of these responses to a low dose of PAF-acether (150 ng X kg-1). CV3988 itself was found to cause a fall in both BP and platelet count in vivo. Collagen (40 micrograms X kg-1) i.v. caused sudden death in rabbits and pretreatment with CV3988 (5 mg X kg-1) caused a 62% inhibition of the platelet count response to collagen without significantly increasing the survival rate. In the rat, collagen (40 micrograms X kg-1) was not lethal and CV3988 caused a dose-dependent inhibition of the fall in platelet count due to collagen, but this action was short-lived. CV3988 also caused agonist actions in the rat. These results show that CV3988 inhibits the effects of PAF-acether in vivo and suggests that PAF-acether may play a role in mediating collagen-induced platelet aggregation in vivo.