Abstract
The H1-histamine receptor antagonist Dithaden® inhibited in a dose-dependent manner, human platelet aggregation in vitro that was induced with stimuli in the following rank order of potency: thrombin > A23187 > adrenaline > ADP. The aggregation of platelets in plasma induced with adrenaline was inhibited by Dithiaden (DIT) (both the first and the second phase) and the onset of the second phase was prolonged significantly. In a concentration-dependent manner DIT inhibited thrombin- and calcium ionophore A23187-induced [3H]arachi-donic acid liberation from, and peroxidation (measured as malondialdehyde formation) of membrane phospholipids. The same effect of DIT was found for the inhibition of thromboxane B2 generation. It is suggested that DIT does not inhibit stimulated platelets at specific histamine receptors sites but rather at the phospholipase A2 and thromboxane synthase level. Results from in vitro experiments should be verified in vivo.
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