What question did this study set out to answer?

Determine whether clopidogrel inhibits platelet activation in vivo by blocking the adenylate cyclase-coupled ADP receptor or the aggregation-mediating membrane protein aggregin.

April 1, 1992Arteriosclerosis and Thrombosis A Journal of Vascular BiologyOpen Access

Clopidogrel inhibits the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase.

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Why the study?

Does clopidogrel inhibit the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase in human subjects?

Population

6 human subjects

Comparison

Clopidogrel 75 mg/day for 10 days vs Placebo (double-blind crossover design)

Design

RCT, crossover experiment, double-blind

Follow-up

10 days per treatment period

Authors

DMD. C. B. MillsUniversity of Iowa CHChang-Jun HuThomas Jefferson University CMCaterina P. MinnitiMemorial Hospital of South Bend

Discussion

Member takes

Implication

Clopidogrel inhibits platelet ADP receptor binding in humans; confirms its mechanism and supports targeted P2Y12 inhibition in practice and trials.

Key Points

Determine whether clopidogrel inhibits platelet activation in vivo by blocking the adenylate cyclase-coupled ADP receptor or the aggregation-mediating membrane protein aggregin.
Conducted a double-blind crossover experiment in six human subjects (N=6) receiving clopidogrel (75 mg/day for 10 days) or placebo.
Evaluated bleeding time, ADP- and thrombin-induced platelet aggregation, shape change, [3H]FSBA labeling of aggregin, and [32P]2-MeSADP binding and adenylate cyclase activity.
Clopidogrel significantly impaired ADP- and thrombin-induced platelet aggregation and prolonged bleeding times in all subjects, while platelet shape change and aggregin labeling remained unaffected.
Inhibition of adenylate cyclase by ADP and 2-MeSADP was substantially reduced, showing noncompetitive antagonism with respect to 2-MeSADP without affecting epinephrine-mediated inhibition.
[32P]2-MeSADP platelet binding sites decreased from 534 ± 44 molecules per platelet during control/placebo periods to 199 ± 78 during clopidogrel treatment (N=3), with no consistent change in binding affinity.

Structured PICO

Does clopidogrel inhibit the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase in human subjects?

Population

6 human subjects

Intervention

Clopidogrel 75 mg/day for 10 days

Comparator

Placebo (double-blind crossover design)

Outcome

Binding of ADP analogues to platelet receptors and inhibition of adenylate cyclasesurrogate

Clopidogrel exerts its antiplatelet effect by inhibiting the high-affinity binding site for ADP linked to the inhibition of stimulated adenylate cyclase.

Cite This Study

Mills et al. (1992) studied this question.

synapsesocial.com/papers/6a7d8933d0946debe914fdc5 https://doi.org/10.1161/01.atv.12.4.430

Topics

Dual antiplatelet therapy

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Implication

Clopidogrel inhibits platelet ADP receptor binding in humans; confirms its mechanism and supports targeted P2Y12 inhibition in practice and trials.

Clopidogrel inhibits the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Clopidogrel inhibits the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

Also Consider