Summary
Ticlopidine is thought to be a selective inhibitor of ADP-induced platelet function.
Here we have investigated the effects of ticlopidine on platelet function in whole
blood induced by ADP and by other platelet agonists. Whole blood was used because
it was considered that ADP derived from red cells might act synergistically with other
platelet agonists to enhance platelet responses, and that ticlopidine might interfere
with this process. Measurements were performed using blood from 16 healthy volunteers
before ticlopidine administration, after taking ticlopidine 250 mg daily for 10 days,
after taking ticlopidine 250 mg twice daily for a further 10 days, and after 14 days
off treatment.
Ticlopidine proved to be a very effective inhibitor of the platelet aggregation induced
by ADP; it was most effective in enhancing the reversibility of the aggregation response.
The drug modestly but significantly reduced streptokinase, adrenaline, collagen, sodium
arachidonate, PAF and U46619 – induced platelet aggregation. The drug significantly
reduced the extent of the release reaction (14C-5HT release) induced by ADP, streptokinase, PAF, ristocetin and sodium arachidonate,
and also reduced the extent of the synergistic 14C-5HT release induced by combinations of ADP and PAF, ADP and adrenaline and PAF and
adrenaline.
The various inhibitory effects of ticlopidine were evident after treatment with 250
mg daily but were more pronounced after 250 mg twice daily. All values had returned
to normal after 14 days off treatment. Ticlopidine had no effect on serum thromboxane
B2 production nor on several parameters of coagulation and fibrinolysis.
We conclude that ticlopidine is an effective inhibitor of ADP-induced platelet aggregation
and also the platelet aggregation and 14C-5HT release induced in whole blood by a number of platelet agonists and combinations
of agonists. These latter effects are probably mainly via a selective effect on ADP.
The inhibitory effects of the drug are dose-related.
