Clopidogrel is an
antiplatelet drug which has undergone extensive clinical trials in the management of
stroke and other arterial disorders related to platelet activation. This agent is believed to produce the inhibition of
ADP mediated direct and indirect actions leading to platelet adhesion/aggregation and other activation processes. Several other observed
pharmacologic actions suggest that this
drug may have additional sites of action.
Ticlopidine also belongs to the same class of
ADP receptor inhibitors and is extensively used for
stroke prevention. To study the vasomodulatory action of
clopidogrel and
ticlopidine, the drugs were administered intravenously into canines at a dose of 10 mg/kg. Thirty minutes later femoral and pulmonary arteries were removed and taken for isolated tissue preparations. The
intravenous injection of
clopidogrel and
ticlopidine caused significant vasomodulatory actions in both femoral and pulmonary ring preparations showing a marked desensitization to
serotonin,
endothelin-1, serum, and platelet rich plasma/
arachidonic acid mixtures. In contrast, when the drugs were added directly to the organ bath containing femoral or pulmonary ring preparations from untreated animals, both
clopidogrel and
ticlopidine did not produce any effect on contractile response induced by
serotonin,
endothelin-1, serum, and platelet rich plasma/
arachidonic acid mixtures. These data suggest that endogenous transformation of
clopidogrel and
ticlopidine plays an important role in producing their vasomodulatory actions. Furthermore, these observations indicate that both
clopidogrel and
ticlopidine also modulate the vascular sites which may be contributory to the observed clinical effects.