10.6084/m9.figshare.5126389.v1
Knorr M.
Knorr
M.
Hausding M.
Hausding
M.
Pfeffer A.
Pfeffer
A.
Jurk K.
Jurk
K.
Jansen T.
Jansen
T.
Schwierczek K.
Schwierczek
K.
Oelze M.
Oelze
M.
Kröller-Schön S.
Kröller-Schön
S.
Schulz E.
Schulz
E.
Wenzel P.
Wenzel
P.
Supplementary Material for: In vitro and in vivo Characterization of a New Organic Nitrate Hybrid Drug Covalently Bound to Pioglitazone
Karger Publishers
2014
Vascular function
Nitric oxide donors
Organic nitrates
Hybrid molecules
Nitrate tolerance
Platelet aggregation
Oxidative stress
2014-06-07 00:00:00
Dataset
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_In_vitro_and_in_vivo_Characterization_of_a_New_Organic_Nitrate_Hybrid_Drug_Covalently_Bound_to_Pioglitazone/5126389
<b><i>Background/Aims:</i></b> Organic nitrates represent a group of nitrovasodilators that are clinically used for the treatment of ischemic heart disease. The new compound CLC-3000 is an aminoethyl nitrate (AEN) derivative of pioglitazone, a thiazolidinedione antidiabetic agent combining the peroxisome proliferator-activated receptor γ agonist activity of pioglitazone with the NO-donating activity of the nitrate moiety. <b><i>Methods:</i></b> In vitro and in vivo characterization was performed by isometric tension recording, platelet function, bleeding time and detection of oxidative stress. <b><i>Results:</i></b> In vitro, CLC-3000 displayed more potent vasodilation than pioglitazone alone or classical nitrates. In vitro, some effects on oxidative stress parameters were observed. Authentic AEN or the AEN-containing linker CLC-1275 displayed antiaggregatory effects. In vivo treatment with CLC-3000 for 7 days did neither induce endothelial dysfunction nor nitrate tolerance nor oxidative stress. Acute or chronic administration of AEN increased the tail vein bleeding time in mice. <b><i>Conclusion:</i></b> In summary, the results of these studies demonstrate that CLC-3000 contains a vasodilative and antithrombotic activity that is not evident with pioglitazone alone, and that 7 days of exposure in vivo showed no typical signs of nitrate tolerance, endothelial dysfunction or other safety concerns in Wistar rats.