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01 January 2002

Effect of diazepam and clonazepam on the function of isolated rat plateletand neutrophil.

Dorota Zółkowska, Grazyna Rajtar, Zdzisław Kleinrok

Med Sci Monit 2002; 8(4): PI37-44 :: ID: 420858


BACKGROUND: Benzodiazepine binding sites distinct from the GABA-receptor-chloride-complexin the central nervous system have been recognized in many peripheral tissues, but their physiologicalrole remains unexplained. Our study was undertaken to examine the effects of diazepam, clonazepam, andPK 11195, a peripheral benzodiazepine receptor antagonist, on the functional and biochemical responsesof platelets and neutrophils stimulated by different physiological agonists. MATERIAL/METHODS: The experimentswere conducted on isolated washed rat platelets activated by arachidonic acid (AA), adenosine 5'-diphosphate(ADP), or thrombin and on isolated rat neutrophils activated by a chemotactic peptide, formyl methionylleucyl phenylalanine (fMLP). RESULTS: The results showed that neither diazepam nor clonazepam nor PK11195 alone augmented the response of resting platelets or modified neutrophil response, but diazepamand clonazepam in a concentration-dependent manner inhibited thrombin, ADP or AA-stimulated plateletaggregation and the thrombin-induced increase in free intracellular Ca2+. Both drugs also exerted aninhibitory effect on reactive oxygen species (ROS) produced by fMLP-stimulated neutrophils. However,diazepam was about 10 times more effective than clonazepam. PK11195 did not influence platelet and neutrophilfunction stimulated by agonists, but reversed the inhibitory action of both benzodiazepines on plateletactivation and ROS production. CONCLUSIONS: The results indicated that in vitro diazepam, and in a muchsmaller degree clonazepam, may down-regulate platelet activation and release of some proinflammatorymediators by stimulated neutrophils. These effects are probably exerted by a specific benzodiazepinebinding sites.

Keywords: Adenosine Diphosphate, Alprostadil, Arachidonic Acid, Blood Platelets, Calcium Signaling, clonazepam, Diazepam, Drug Interactions, Isoquinolines, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, Platelet Activation, Platelet Aggregation Inhibitors, Rats, Wistar, Receptors, GABA-A, Respiratory Burst, Thrombin

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750