1996
DOI: 10.1177/107602969600200108
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Clopidogrel: An Antithrombotic Drug Acting on the ADP-dependent Activation Pathway of Human Platelets

Abstract: The aim of the study was to determine the effect of clopidogrel on adenosine diphosphate (ADP)-induced platelet activation in human volunteers. Platelets from human volunteers before and after a 7-day treatment with clopidogrel (75 mg/kg), were tested for their sensitivity to ADP by measuring ADP-induced aggregation, adenylyl cyclase downregulation, and [ 3 H]-2-MeS-ADP binding. Platelet membrane glycoprotein (GP IIb-IIIa; GP Ib, GMP-140) expression was measured by flow cytometry using fluorescent-labeled anti… Show more

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Cited by 57 publications
(39 citation statements)
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“…9 Clopidogrel and the chemically related ticlopidine are thienopyridines that selectively and specifically interfere with ADP-mediated platelet activation. 5,10 In contrast to ticlopidine, which may cause neutropenia, clopidogrel appears to be a safe and well-tolerated drug. 9 Thienopyridines are inactive in-vitro, require in vivo metabolism, and cause an irreversible inhibition of platelet function.…”
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confidence: 99%
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“…9 Clopidogrel and the chemically related ticlopidine are thienopyridines that selectively and specifically interfere with ADP-mediated platelet activation. 5,10 In contrast to ticlopidine, which may cause neutropenia, clopidogrel appears to be a safe and well-tolerated drug. 9 Thienopyridines are inactive in-vitro, require in vivo metabolism, and cause an irreversible inhibition of platelet function.…”
mentioning
confidence: 99%
“…[13][14][15][16][17][18][19][20] Earlier studies with ticlopidine and clopidogrel had suggested that thienopyridines do not inhibit the ADP receptor pathways coupled to calcium influx and mobilization but instead, prevent the inhibitory ADP effects on adenylyl cyclase stimulation in platelets of different species. 10,15,16,[21][22][23][24][25] In the current study, we addressed the question as to which of the 3 now pharmacologically defined human platelet ADP receptors is affected by a clinically used clopidogrel dosage. Moreover, we analyzed the effect of clopidogrel on ADPregulated intracellular signaling and protein phosphorylation.…”
mentioning
confidence: 99%
“…The other one is a low-affinity receptor of which activation by ADP results in the down-regulation of activated adenylyl cyclase, activation of the Gp IIb-IIIa complex and platelet aggregation. Clopidogrel, a thienopyridinic antiaggregating compound, has been demonstrated to antagonize ex vivo the binding of ADP to its low-affinity receptors without interfering with the effects of ADP on the other binding site which mediates shape change (Mills et al, 1992;Savi et al, 1994bSavi et al, , 1996.…”
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confidence: 99%
“…Similar affinities for both receptors were found for most of them including adenosine, AMP, ADP, ATP, a,b-Me-ADP, ATPgS, FSBA and PPADS. However the affinity of 2-MeS-ADP for [ We then used clopidogrel, a thienopyridine which has already been shown to strongly inhibit 2-MeS-ADP-or ADPinduced platelet aggregation, inhibition of PGE1-stimulated adenylyl cyclase and binding of [ 3 H]2-MeS-ADP to platelets isolated from treated animals and humans (Defreyn et al, 1991;Savi et al, 1994bSavi et al, , 1996. When we examined the ex vivo effect of clopidogrel on [ 33 P]2-MeS-ADP binding to rat platelets, Scatchard analysis revealed that clopidogrel behaved as an irreversible, non-competitive inhibitor, as previously found with [ 3 H]2-MeS-ADP (Savi et al, 1994b).…”
mentioning
confidence: 99%
“…ADP induces shape change in platelets and Ca2+-influx, processes that occur independently of platelet aggregation. Studies using ticlopidine and its more recent analogue, clopidogrel, have shown that administration of these drugs results in a limited and highly reversible aggregation at even the highest dose of ADP (11,13). At the maximal peak of aggregation, the aggregates are composed of low numbers of loosely packed platelets (14).…”
Section: Platelet Activation Mechanismsmentioning
confidence: 99%