title: Benzodiazepine analogues inhibit arachidonate-induced aggregation and thromboxane synthesis in human platelets.
abstract: 1. Benzodiazepine analogues inhibit human platelet aggregation induced by arachidonate with an EC50 value of 0.68 microM for PK 11195, the most potent analogue used. 2. There was a highly significant correlation between the inhibition of arachidonate-induced aggregation and the affinity for the peripheral-type of benzodiazepine binding sites. 3. There was no significant correlation between the inhibition of the platelet activating factor (PAF)-induced aggregation and the binding to the peripheral-type of benzodiazepine binding sites. 4. The inhibition of platelet aggregation seems to result from the inhibition of arachidonic acid cyclo-oxygenation, since the synthesis of thromboxane and 12-hydroxy-heptadecatrienoic acid, both cyclo-oxygenase products, was reduced. 5. Our results suggest that peripheral-type of benzodiazepine binding sites on human platelets could be linked to cyclo-oxygenase.
authors.affiliation: Unité INSERM 205-Laboratoire de Chimie Biologique, Villeurbanne, France.
authors.forename: P
authors.initials: P
authors.lastname: Fonlupt
authors.forename: M
authors.initials: M
authors.lastname: Croset
authors.forename: M
authors.initials: M
authors.lastname: Lagarde
mesh_terms: D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000378:metabolism; D007700:Kinetics; D010972:Platelet Activating Factor; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects; D013931:Thromboxanes / Q000096:biosynthesis*
chemical_list: D001095:Arachidonic Acids; D001779:Blood Coagulation Factors; D016861:Cyclooxygenase Inhibitors; D007546:Isoquinolines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011963:Receptors, GABA-A; D013931:Thromboxanes; D001569:Benzodiazepines; D016718:Arachidonic Acid; C037850:PK 11195