Vasomodulatory action of clopidogrel and ticlopidine

Clopidogrel is a thienopyridine derived antiplatelet drug that has currently undergone extensive clinical trials in the management of various arterial disorders related to platelet activation. While the proposed mechanism of its pharmacologic action is believed to be the inhibition of ADP mediated direct and indirect actions on platelet adhesion/aggregation and other activation processes, several other observed pharmacologic actions suggest that this drug may also have additional sites of action. Ticlopidine also belongs to the same class of ADP receptor inhibitor and is extensively used for prevention of ischemic disorders. In order to investigate the vasomodulatory action of clopidogrel and ticlopidine, rabbit and rat isolated tissue preparation systems were used. Clopidogrel and ticlopidine were found to produce dose dependent vasomodulatory actions in rabbit or rat treated with 30 minutes intravenous administration. The aortas harvested from both the rabbits and rats treated with clopidogrel or ticlopidine exhibited marked desensitization to the serotonin, endothelin-1, serum and platelet rich plasma/arachidonic acid mixtures. Both control rabbit aortic rings and rat aortic strips did not produce any inhibition of the serotonin induced contraction. These data suggest that clopidogrel and ticlopidine plays an important role in producing these vasomodulatory actions. Furthermore these observations indicate that both the clopidogrel and ticlopidine also modulate the vascular sites which may be contributory to the observed clinical effects.