A new nitrate derivative of piperazine: its influence on platelet activity

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Abstract

Nitric oxide (NO) is a potent vasodilator and inhibitor of platelet activation. Its donors, organic nitrates, are still a main group of drugs administered in ischaemic heart disease. The aim of this study was to investigate the effect of a new NO-donor analogue, 1-(3-piperidinepropionyl)-4-(2-nitrooxy-3-piperidinepropyl) piperazine trihydrochloride (NO-P), on platelet activity. Its influence on the main mechanisms of human platelet activation (adhesion, shape change, secretion and aggregation) was evaluated with the use of a pharmacological model produced on the basis of known platelet activation measuring methods and our computer program. Our experiments revealed that the new NO derivative of piperazine favourably influences platelet activity, and decreases adhesion (spontaneous and induced by ADP) and aggregation. NO-P shows the same direction of action as nitroglycerin (used as a model compound), and is even stronger in the case of ADP-induced and collagen-induced aggregation. These findings broaden the possibility of using NO-P in cardiovascular diseases. Furthermore, our computer program, used to evaluate kinetic parameters of platelet aggregation, shape change, and the adhesion measuring method, provides a simple and accessible experimental model. This model can be useful in in-vitro screening studies, estimating the influence of new compounds (potential drugs) on platelet activity.

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