Antithrombotic effects of morpholine and piperazine ring derivatives and their molecular mechanism.
- Author:
Dong-mei CHEN
1
;
Kai CHEN
;
Hai WANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Aorta, Thoracic; Endothelium, Vascular; drug effects; metabolism; Female; Fibrinolytic Agents; pharmacology; Male; Mice; Morpholines; pharmacology; Piperazines; pharmacology; Plasminogen Activator Inhibitor 1; metabolism; Platelet Aggregation; drug effects; Rats; Rats, Wistar; Tissue Plasminogen Activator; metabolism; Vasodilator Agents; pharmacology
- From: Acta Pharmaceutica Sinica 2003;38(9):641-645
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo investigate the antithrombotic effects of morpholine and piperazine ring derivatives and their mechanisms.
METHODSIn 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.
RESULTS AND CONCLUSIONActive 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).
