In vitro study of the anti-aggregating activity of two nitroderivatives of acetylsalicylic acid.
The antiplatelet activity of two new nitrocompounds, chemically related to acetylsalicylic acid (NCX 4215 and NCX 4016), was studied in vitro to verify the hypothetical dual action of these drugs. Both drugs, in a dose-dependent way, inhibited arachidonic acid-induced platelet aggregation and thromboxane A2 production, measured as thromboxane B2 concentration in whole blood. These effects are likely to be related to cyclo-oxygenase inhibition. NCX 4215 and NCX 4016 in a dose-dependent way inhibited also thrombin-induced aggregation of platelets pretreated with acetylsalicylic acid. These inhibitory effects are related to nitric oxide release and cGMP increase and significantly reversed by oxyhaemoglobin and methylene blue. Either as a cyclo-oxygenase inhibitor or as a nitric oxide donor, NCX 4016 proved to be significantly more potent than NCX 4215.
Lechi
C
C
Institute of Clinical Chemistry, University of Verona, Italy.
Gaino
S
S
Tommasoli
R
R
Zuliani
V
V
Bonapace
S
S
Fontana
L
L
Degan
M
M
Lechi
A
A
Minuz
P
P
D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; C098730:NCX 4215; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D009569:Nitric Oxide; D013929:Thromboxane B2; D013928:Thromboxane A2; D013917:Thrombin; C102148:nitroaspirin; D001241:Aspirin