New NO donors with antithrombotic and vasodilating activities, Part 24. Hydrazine derivatives.
Suitable hydrazines like phenylhydrazine (1), N,N-dimethyl hydrazine (4), and N,N-diphenyl hydrazine (5) can be oxidized by hydrogen peroxide at pH 7.4 and 37 degrees C to nitrosohydrogen and further to nitrite and nitrate. The extent of this property is correlated with platelet aggregation inhibiting and antithrombotic effects of these compounds, suggesting that an NO mediated mechanism might be involved. All hydrazines tested and two N-ethoxycarbonyl prodrugs exhibited antihypertensive effects which were not correlated to the above properties. This is especially pronounced in hydralazine (6) and dihydralazine (7) which induced a strong decrease in blood pressure but exhibit neither antiplatelet nor antithrombotic effects. This indicates that the mechanism of the antihypertensive activity is different from that of the antiplatelet activity.
Rehse
K
K
Institut für Pharmazie I, Freie Universität Berlin, Germany.
Shahrouri
T
T
D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D020030:Nitric Oxide Donors / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D005343:Fibrinolytic Agents; D006834:Hydrazines; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents