January 9, 2013
Common Antidepressant Drug Could Prevent
Galveston, TX—The commonly used antidepressant drug paroxetine has the potential to be a valuable therapy for the vascular complications of diabetes.
That's according to researchers from the University of Texas Medical Branch (UTMB) at Galveston, who made the discovery after screening 6,766 clinically used drugs and pharmacologically active substances. Their report was published online recently by the journal Diabetes.
“We developed this assay and used it to test literally every single existing drug and a good selection of other biologically active compounds," said senior author Csaba Szabo, MD, PhD, a professor at UTMB. “We were quite surprised when paroxetine came out as an active compound—a result, we later determined, of what seems to be a completely new effect unrelated to its antidepressant actions and not shared by any other known antidepressant drug."
The initial screening process tested the ability of different compounds to protect the cells that make up the inner linings of blood vessels from the destructive effects of hyperglycemia, which causes endothelial cells to generate reactive oxygen species (ROS). Those toxic molecules lead to diabetic endothelial dysfunction, which can result in heart attacks, strokes, retinopathy, nephropathy, and neuropathy.
After additional test-tube studies, researchers found that paroxetine, marketed as Paxil, prevents hyperglycemia-initiated ROS damage to endothelial cells by both directly reducing concentrations of superoxide, a powerful ROS, and by suppressing superoxide production by mitochondria.
Furthermore, paroxetine appeared to inhibit this activity without affecting the normal function of the mitochondria.
Animal studies showed further benefits of paroxetine, the researchers said.
The authors note that the antidepressant compound has not previously been recognized as an effective agent in terms of hyperglycemia or diabetes, and that “the ability of paroxetine to improve hyperglycemic endothelial cell injury was unique among serotonin reuptake blockers and can be attributed to its antioxidant effect, which primarily resides within its sesamol moiety.”
“The future potential of this study is that we may be able to 're-purpose' paroxetine for the experimental therapy of diabetic cardiac complications," Szabo said. “We'll need to carefully characterize its safety profile in diabetic patients, but I think there's definite potential here.”
|U.S. Pharmacist Social Connect