Benzodiazepine analogues inhibit arachidonate‐induced aggregation and thromboxane synthesis in human platelets

Abstract

Benzodiazepine analogues inhibit human platelet aggregation induced by arachidonate with an EC50 value of 0.68 μm for PK 11195, the most potent analogue used. There was a highly significant correlation between the inhibition of arachidonate‐induced aggregation and the affinity for the peripheral‐type of benzodiazepine binding sites. 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. The inhibition of platelet aggregation seems to result from the inhibition of arachidonic acid cyclooxygenation, since the synthesis of thromboxane and 12‐hydroxy‐heptadecatrienoic acid, both cyclooxygenase products, was reduced. Our results suggest that peripheral‐type of benzodiazepine binding sites on human platelets could be linked to cyclo‐oxygenase.

Lack of inhibitory effect of acetylsalicylic acid and meloxicam on whole blood platelet aggregation in cats

“…It is known that benzodiazepine receptors exist on platelets and diazepam results in less platelet inhibition than most other drugs in its class . Benzodiazepine‐associated inhibition is directly correlated with decreases in arachidonic acid metabolite production, and it is believed that diazepam has inhibitory effect on the COX and lipoxygenase enzymes . It is therefore possible that the diazepam used for sedation in our study had some influence in decreasing TXB 2 concentrations.…”

“…The potential effects of the sedatives used for blood collection in this study should be considered. Many anesthetic drugs can inhibit platelet aggregation, although diazepam has conflicting reports of either inhibitory effects or no effect . It is known that benzodiazepine receptors exist on platelets and diazepam results in less platelet inhibition than most other drugs in its class .…”

“…Many anesthetic drugs can inhibit platelet aggregation, although diazepam has conflicting reports of either inhibitory effects or no effect . It is known that benzodiazepine receptors exist on platelets and diazepam results in less platelet inhibition than most other drugs in its class . Benzodiazepine‐associated inhibition is directly correlated with decreases in arachidonic acid metabolite production, and it is believed that diazepam has inhibitory effect on the COX and lipoxygenase enzymes .…”