Action of some salicylate derivatives on in vitro platelet aggregation. Inhibitory and inhibition antagonistic effects.
Twenty salicylate derivatives were tested for their antagonistic activity on the inhibitory effect of aspirin on platelet aggregation. The blocking effect was not limited to the salicylate but also characterised some of its substituted compounds. The substituant influence did not seem to be related to electronic or size parameters. This antagonistic activity of these derivatives decreased as concentrations increased, owing to the emergence of their own inhibitory activity: several salicylate derivatives showed dual inhibitory and inhibition antagonistic activity, with both properties present at the same concentration. A mechanism involving dissociated activities on the two enzymatic sites of cyclooxygenase is proposed.
Casadebaig
F
F
Faculté de Pharmacie, Université de Bordeaux II, France.
Dupin
J P
JP
Gravier
D
D
Hou
G
G
Daret
D
D
Bernard
H
H
Larrue
J
J
Boisseau
M
M
D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012459:Salicylates / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; D016718:Arachidonic Acid; D001241:Aspirin