Effects of subacute treatment with benzopyranopyrimidines in hemostasis and experimental thrombosis in mice.
The antithrombotic activity of a series of benzopyranopyrimidine derivatives was investigated in platelet-dependent and independent pulmonary thromboembolism in mice. Intraperitoneal subacute treatment with 2-morpholino derivative 3c significantly prevented paralysis due to collagen plus epinephrine-induced pulmonary thrombosis while 2-piperidino substituted derivative 3h significantly protected mice from paralysis caused by thrombin-induced intravascular fibrin formation at dosage not affecting bleeding time. These compounds, previously proved to be effective as antiplatelet agents in vitro, were in vivo more potent as antithrombotics than lysine acetylsalicylate and possessed lower prohemorrhagic activity than the reference drug. Although their ineffectiveness on clotting times, PT and APTT, allows the involvement of coagulation pathways to be ruled out, the mechanisms underlying the favourable benefit risk ratio for these two compounds remain to be further clarified.
Ballabeni
Vigilio
V
Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate, Università di Parma, Parco Area delle Scienze 27/A, 43100 Parma, Italy.
Calcina
Francesco
F
Tognolini
Massimiliano
M
Bruno
Olga
O
Manotti
Cesare
C
Barocelli
Elisabetta
E
D000818:Animals; D006487:Hemostasis / Q000187:drug effects*; D051379:Mice; D010243:Paralysis / Q000188:drug therapy; D010437:Peptic Ulcer / Q000188:drug therapy; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011655:Pulmonary Embolism / Q000188:drug therapy*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D010975:Platelet Aggregation Inhibitors; D011743:Pyrimidines