ABSTRACT
After p.o. administration to rats in doses up to 30 mg/kg, Viagra showed no antithrombotic effect. However, it enhanced the inhibition of thrombus formation by RE 2047 from 9% to 17% (5 + 5 mg/kg) or 19% to 27% (10 + 10 mg/kg) in arterioles. This effect was even more obvious in venules where an inhibition of 9% (5 + 5 mg/kg) or 15% (10 + 10 mg/kg) was seen whereas the individual drugs had no effect. The antithrombotic activity of molsidomine was not altered. The blood pressure (b.p.) of spontaneously hypertensive rats was reduced by the combination of Viagra and RE 2047 (5 + 5 mg/kg) to 94% of normal after 2 h while the individual drugs had no effect at this dose. The coadminstration of 10 mg/kg of each drug reduced the b.p. to 87% of normal. The combination of Viagra with molsidomine decreased b.p. to 84% (5 + 5 mg/kg) or 79% (10 + 10 mg/kg), respectively.
Subject(s)
Blood Pressure/drug effects , Fibrinolytic Agents/pharmacology , Hypertension/physiopathology , Molsidomine/pharmacology , Nitric Oxide Donors/pharmacology , Phosphodiesterase Inhibitors/pharmacology , Piperazines/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Sydnones/pharmacology , Animals , Arterioles/drug effects , Arterioles/pathology , Drug Interactions , Hypertension/drug therapy , Purines , Rats , Rats, Inbred SHR , Sildenafil Citrate , Sulfones , Thrombosis/pathology , Thrombosis/prevention & control , Venules/drug effects , Venules/pathologyABSTRACT
Five 1,3,4-triazol-1-oles (5a-f) with different alkyl, aryl, and arylalkyl substituents in 2,5-position were synthesized and tested for their antithrombotic properties. The 2,5-dimethyl derivative 5a was most active. 2 h after administration of 60 mg/kg to rats thrombus formation by a laser beam was inhibited by 42% in arterioles and by 33% in venules. At the same dose the blood pressure of SHR rats was slightly (5%) but significantly decreased even 4 h after application of 5a. This pattern of activities suggests a nitric oxide mediated mechanism of action. 1,1'-Azo-bis-ethanone oxime(7)-the synthetic precursor of 5a-inhibited the aggregation of blood platelet (Born test) with an IC50 = 15 mumol/L.
