DN 9693: a phosphodiesterase inhibitor with a platelet membrane effect.
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 Ib (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.
Jackson
C
C
Department of Haematology, Royal Hallamshire Hospital, Sheffield, UK.
Ball
J
J
Peel
J
J
Lawry
J
J
Greaves
M
M
Preston
F E
FE
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D000242:Cyclic AMP / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D012310:Ristocetin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011799:Quinazolines; D012310:Ristocetin; D012701:Serotonin; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; C049662:1,5-dihydro-7-(1-piperidinyl)-imidazo(2,1-b)quinazolin-2(3H)-one; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases