Glitazones (
thiazolidinediones) are drugs used for
diabetes mellitus type 2. By binding to
peroxisome proliferator-activated receptor γ (PPARγ) they modulate transcription of genes of
carbohydrate and lipid metabolism. Through PPARγ stimulation, however,
glitazones also affect other genes, encompassing
inflammation, cell growth and differentiation, angiogenesis, which broads their therapeutic potential. The gene expression profile induced by each glitazone shows peculiarities, which may affect its benefit/risk balance; indeed,
troglitazone and
rosiglitazone have been associated with
liver failure and
coronary disease, respectively; whether or not these severe adverse effects are solely related to PPARγ remains yet unclear, since
glitazones exert also PPARγ-independent effects. Glitazone chemistry serves as scaffold for synthesizing new compounds with PPARγ-independent pharmacological properties and we report here a preliminary observation of inhibition of vasoconstriction by
troglitazone in isolated vessels, an effect that appears fast, reversible, and PPARγ-independent. Pleiotropic effects of
glitazones need specific attention in terms of
drug safety, but also provide basis for
drug development and novel experimental
therapeutics.