Comparison of anti-platelet properties of molsidomine, isosorbide-5-mononitrate and placebo in healthy volunteers.
The purpose of the present work was to investigate the ex vivo platelet-inhibiting properties of the nitric oxide-containing vasodilator, molsidomine, and the organic nitrate, isosorbide-5-mononitrate, in comparison with placebo. Ex vivo platelet aggregation in 11 healthy volunteers was measured before, as well as 30 and 60 min after, the intake of either 4 mg molsidomine, 20 mg isosorbide-5-mononitrate (ISMN) or placebo in a randomized double-blind fashion. The release of thromboxane was also determined. Threshold doses of platelet-activating factor (PAF) to induce irreversible aggregation were significantly increased by 100 and 120% 30 and 60 min after molsidomine. Slopes of aggregation curves (aggregation induced with 50 and 200 nM PAF) were significantly reduced after molsidomine (P less than 0.01). Small platelet-inhibiting effects were also observed after ISMN and after placebo intake. The release of thromboxane was not influenced when platelets were maximally stimulated either during clotting of whole blood or during aggregation of platelet-rich plasma with a high dose of PAF. Thromboxane release with a low dose of PAF was reduced 30 and 60 min after drug intake, independent of whether molsidomine, ISMN or placebo was applied. The data indicate that the usual clinical doses of molsidomine, but not of ISMN inhibit platelet aggregation in healthy man.
Drummer
C
C
Medizinische Klinik, Klinikum Innenstadt der Universität, München, Germany.
Valta-Seufzer
U
U
Karrenbrock
B
B
Heim
J M
JM
Gerzer
R
R
D000328:Adult; D001760:Bleeding Time; D006152:Cyclic GMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000097:blood / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors; D011897:Random Allocation; D012016:Reference Values; D013929:Thromboxane B2 / Q000097:blood
D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D008981:Molsidomine; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate