Rosiglitazone maleate

Rosiglitazone maleate is the maleic acid salt form of rosiglitazone, a potent insulin sensitizer, which is used for the treatment of diabetes. Rosiglitazone belongs to a group of compounds, thiazolidinediones (TZDs), which selectively ligate the nuclear transcription factor peroxisome-proliferator-activated receptor-γ (PPARγ). As a TZD, rosiglitazone improves the sensitivity of end organs to insulin through PPARγ activation which poteniates them to lower concentrations of blood glucose. Despite of its beneficial effects of targeting insulin resistance, recent studies has shown that rosiglitazone is associated with several moderate to severe adverse effects, including hemodilution, anemia, weight gain, and edema as well as increased risk for heart failure and myocardial ischemic events.(In Vitro):Rosiglitazone maleate is a potent and selective activator of PPARγ, with EC50s of 30 nM and 100 nM for PPARγ1 and PPARγ2, respectively, and a Kd of appr 40 nM for PPARγ. Rosiglitazone (BRL49653, 0.1, 1,10 μM) promotes differentiation of C3H10T1/2 stem cells to adipocytes. Rosiglitazone (Compound 6) activates PPARγ, with an EC50 of 60 nM. Rosiglitazone (1 μM) activates PPARγ, which binds to NF-α1 promoter to activate gene transcription in neurons. Rosiglitazone (1 μM) also protects Neuro2A cells and hippocampal neurons against oxidative stress, and up-regulates BCL-2 expression in an NF-α1-dependent manner. Rosiglitazone completely inhibits TRPM3 with IC50 values of 9.5 and 4.6 μM against nifedipine- and PregS-evoked activity, but such effects are not via PPARγ. Rosiglitazone inhibits TRPM2 at higher concentration, with an IC50 of appr 22.5 μM. Rosiglitazone is a strong stimulator of TRPC5 channels, with an EC50 of ～30 μM.\n(In Vivo):Rosiglitazone (5 mg/kg, p.o.) decreases the serum glucose in diabetic rats. Rosiglitazone also decreases IL-6 and VCAM-1 levels in diabetic group. Rosiglitazone in combination with losartan increases glucose compared to diabetic and Los-treated groups. Rosiglitazone significantly ameliorates endothelial dysfunction indicated by a significantly lower contractile response to PE and Ang II and enhancement of ACh-provoked relaxation in aortas isolated from diabetic rats.