title: A new nitrate derivative of piperazine: its influence on platelet activity.
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.
authors.affiliation: Department of Pharmaceutical Biochemistry, Medical University of Lodz, Poland. bkostka@pharm.am.lodz.pl
authors.forename: Barbara
authors.initials: B
authors.lastname: Kostka
authors.forename: Joanna
authors.initials: J
authors.lastname: Sikora
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Para
authors.forename: Urszula
authors.initials: U
authors.lastname: Krajewska
authors.forename: Lucyna
authors.initials: L
authors.lastname: Korzycka
mesh_terms: D000244:Adenosine Diphosphate; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D003094:Collagen; D004353:Drug Evaluation, Preclinical; D001330:Electronic Data Processing; D006801:Humans; D007700:Kinetics; D009566:Nitrates / Q000737:chemistry / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects
chemical_list: D009566:Nitrates; D020030:Nitric Oxide Donors; D010879:Piperazines; D000244:Adenosine Diphosphate; D003094:Collagen