[Antithrombotic effects of morpholine and piperazine ring derivatives and their molecular mechanism].
OBJECTIVE
To investigate the antithrombotic effects of morpholine and piperazine ring derivatives and their mechanisms.


METHODS
In isolated rat aorta-precontracted with norepinephrine (NE), the vasodilatory effects of compounds with novel structure were investigated. Mice was given kappa-carrageenin i.p. and kept at the temperature of (20-21) degree C.


CONCLUSIONS
Active candidate compounds including MOPMC, 2FBMPC, MPTMBC, DMHPPP and PPVP were shown to antagonize thrombosis at the dose of 1 mg.kg-1 through activating the endothelial target for acetylcholine; while the contrasting compounds MAPC, 4C3FBMOC, mTBMPC, MONVP and MPNVP showed no significant effect on the tension of isolated aorta strips or significant antithrombotic effects at the same dose. The antithrombotic mechanism of novel compounds is not relevant to hemostatic systems or functions of platelet aggregation directly, but they can promote endothelial cells to release tissue-type plasminogen activator (t-PA) and inhibit the activity of plasminogen activator inhibitor-1 (PAI-1).
Chen
Dong-mei
DM
Institute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850, China.
Chen
Kai
K
Wang
Hai
H
D000818:Animals; D001013:Aorta, Thoracic; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D000077489:Piperazine; D010879:Piperazines / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D005343:Fibrinolytic Agents; D009025:Morpholines; D010879:Piperazines; D017395:Plasminogen Activator Inhibitor 1; D014665:Vasodilator Agents; D000077489:Piperazine; C037574:morpholine; D010959:Tissue Plasminogen Activator