The Action of Ticlopidine on Human Platelets

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Abstract
The effects on platelet function of a 5-day course of Ticlopidine (Tel) have been studied in two groups of volunteers receiving different dosage schedules. Tel had a relatively greater inhibitory effect on aggregation induced by ADP than by other agonists, and a greater effect, in contrast to that of an ADP receptor antagonist, on the second phase than on the initial rate of aggregation. Tel inhibited ATP secretion in response to ADP and 0.05 u/ml thrombin, but not to higher concentrations of thrombin or to calcium ionophores. No inhibitory effect was observed on Ca2+ influx or intracellular mobilization, on the binding of monoclonal antibodies to the glycoprotein IIb-IIIa complex or on the state of association of the complex. We suggest that Tel neither inhibits the binding of ADP to its receptor nor acts directly on the fibrinogen binding site, but that it may inhibit a step in signal transduction between these two events.

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