Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XV: Antithrombotic effect of selected oligoamines in rats.
Oligoamines which exert antiplatelet and anticoagulant properties in vitro show as well antithrombotic effects in mesenteric arterioles and venoles of rats. The formation of thrombi in these vessels was induced by a laser beam and quantified by the thrombus formation index (TFI). The most potent compound RE 1492 already reduced the formation of thrombi after i.v. administration of 1 mg/kg significantly. After oral administration, however, only a minor effect even after a 200 mg/kg dose is observed. This suggests that the oligoamine was poorly absorbed from the gastrointestinal tract. The tricarbamate of RE 1492 (identical to RE 1492 C), however, was a suitable prodrug. Eight hours after a single oral dose of 10 mg/kg significant antithrombotic properties in arterioles and venules were seen. (TFI = 3.63 (A), 1.77 (V); control: 1.76 (A), 1.29 (V).) After p.o. application of 30 mg/kg RE 1492 C the onset of activity is after 2 h (TFI = 3.44/1.48). A maximum effect is reached after 4 h (TFI: 4.43/2.84) and maintained up to 24 h (TFI = 4.49/2.45). After 48 h the effect in arterioles is still significant (p less than 0.05, chi 2-test). The results obtained with five other carbamates (RE 2029 C, RE 1964 C, RE 2120 C, RE 2112 C, and RE 1981 C) 4 h after p.o. administration in general show a stronger effect in arterioles than in venules which is in the same range as in RE 1492 C.
Rehse
K
K
Institut für Pharmazie, Freien Universität Berlin.
Kesselhut
A
A
Schein
V
V
Kämpfe
M
M
Rose
B
B
Unsöld
E
E
D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis*; D005343:Fibrinolytic Agents / Q000138:chemical synthesis*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D000588:Amines; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors