Interaction of Viagra with the NO donors molsidomine and RE 2047 with regard to antithrombotic and blood pressure lowering activities.
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.
Rehse
K
K
Institut für Pharmazie, Freie Universität Berlin, Germany.
Scheffler
H
H
Reitner
N
N
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008981:Molsidomine / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011687:Purines; D051381:Rats; D011918:Rats, Inbred SHR; D000068677:Sildenafil Citrate; D013450:Sulfones; D013558:Sydnones / Q000494:pharmacology*; D013927:Thrombosis / Q000473:pathology / Q000517:prevention & control; D014699:Venules / Q000187:drug effects / Q000473:pathology
C092610:3-methylsydnone-5-nitrosimine; D005343:Fibrinolytic Agents; D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D011687:Purines; D013450:Sulfones; D013558:Sydnones; D000068677:Sildenafil Citrate; D008981:Molsidomine