In:
Pharmacology, S. Karger AG, Vol. 93, No. 5-6 ( 2014), p. 203-215
Abstract:
〈 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 & #947; 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.
Type of Medium:
Online Resource
ISSN:
0031-7012
,
1423-0313
Language:
English
Publisher:
S. Karger AG
Publication Date:
2014
detail.hit.zdb_id:
1483550-2
SSG:
15,3
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