Peripheral benzodiazepine ligands inhibit aggregation and thromboxane synthesis induced by arachidonic acid in rabbit platelets in vitro.

Abstract:

:Seven compounds having varying affinities for peripheral benzodiazepine (p sites) were evaluated in vitro as inhibitors of arachidonic acid-induced rabbit platelet aggregation and thromboxane B2 (TXB2) synthesis. With the exception of flumazenil, all compounds inhibited both parameters with IC50 values ranging from 0.19 to 3.5 microM, with a significant correlation between the inhibition of aggregation and the synthesis of thromboxane B2. The antiaggregatory effect was stereoselective, and inhibition was increased when cellular penetration was favoured by increasing the volume of the organic solvent. The order of potency these compounds is consistent with an effect at intracellular p sites (Ro5-4864 > PK14067 > PK 11195 > PK 14068 > or = clonazepam > or = diazepam > flumazenil). However, the correlation between the aggregation inhibition and the synthesis of TXB2 suggests that microsomal cyclooxygenase may be the intracellular target of these ligands. We therefore propose that this enzyme possesses a site for benzodiazepine ligands which may share certain characteristics with the peripheral benzodiazepine receptor.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Choppin A,Berry CN

doi

10.1016/0049-3848(95)00062-v

subject

Has Abstract

pub_date

1995-05-15 00:00:00

pages

293-302

issue

4

eissn

0049-3848

issn

1879-2472

pii

004938489500062V

journal_volume

78

pub_type

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