We have examined the in vitro effects of DN 9693 (piperidinylimidazo-quinazolinone)
on various aspects of platelet reactivity. Our results are consistent with its known
function as a phosphodiesterase inhibitor in that it increased platelet cyclic AMP,
particularly in conjunction with an adenylate cyclase stimulator, and exerted a profound
inhibitory effect on platelet aggregation responses to a variety of agonists. DN 9693
also inhibited ristocetin-induced platelet agglutination (RIPA). We therefore examined
its effect on ristocetin co-factor assays and on the binding of a monoclonal antibody
(McAb) to platelet membrane glycoprotein lb (GPIb). The drug inhibited the binding
of the monoclonal antibody in a dose-dependent manner. This suggests an effect of
the drug on the platelet surface membrane with reduced expression of GPIb. Our results
indicate that in addition to its anticipated inhibitory effect on platelet aggregation,
DN 9693 may also inhibit platelet adhesion.
Keywords
DN 9693 - Phosphodiesterase inhibitor - Platelet membrane glycoprotein Ib
