Ticlopidine increases nitric oxide generation in heart-transplant recipients: a possible novel property of ticlopidine.

The objective of this study was to evaluate the effects of ticlopidine on the generation of eicosanoids and nitric oxide in heart-transplant recipients. In a randomized double-blind study, we studied the urinary excretion of the stable metabolites of thromboxane, prostacyclin, and nitric oxide before and after ticlopidine (250 mg/day). Platelet aggregation was significantly reduced in ticlopidine-treated patients [from 40.

Effect of various antiplatelet agents on acute arterial thrombosis in the rat.

Electrical stimulation of the rat carotid artery causes a deep medial injury and the formation of a platelet-rich thrombus. Occlusive thrombosis at sites of vessel wall injury was significantly reduced after the oral administration of clopidogrel, a potent analogue of ticlopidine, which showed dose-dependent inhibition of the thrombus formation (ED50 = 1.0 +/- 0.

Inhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits.

The possible activity of ticlopidine and its analogue clopidogrel in early atherogenesis was investigated. Incubation of rabbit platelets with the extracellular matrix produced by endothelial cells in culture induced massive platelet adherence in vitro. This phenomenon was strongly reduced when platelets were isolated from rabbits that had been treated with a single dose of clopidogrel (10 mg/kg PO) or three doses of ticlopidine (each 200 mg/kg PO) (94% and 56% inhibition of platelet adhesion, respectively).

Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel.

The thienopyridine clopidogrel is not active in vitro and must be administered i.v. or orally, suggesting that metabolism is necessary for activity.

Ticlopidine and clopidogrel (SR 25990C) selectively neutralize ADP inhibition of PGE1-activated platelet adenylate cyclase in rats and rabbits.

Ticlopidine and its potent analogue, clopidogrel, are powerful inhibitors of ADP-induced platelet aggregation. In order to improve the understanding of this ADP-selectivity, we studied the effect of these compounds on PGE1-stimulated adenylate cyclase and on the inhibition of this enzyme by ADP, epinephrine and thrombin. Neither drug changed the basal cAMP levels nor the kinetics of cAMP accumulation upon PGE1-stimulation in rat or rabbit platelets, which excludes any direct effect on adenylate cyclase or on cyclic nucleotide phosphodiesterase.