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Antidepressant Doubles as Diabetes Drug

Dec 27, 2012
The commonly used antidepressant drug paroxetine could become a therapy for the vascular complications of diabetes….

The scientists made their discovery after screening 6,766 clinically used drugs and pharmacologically active substances.

"We developed this assay and used it to test literally every single existing drug and a good selection of other biologically active compounds," professor Csaba Szabo, senior author of a paper on the research said in a statement. "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 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 the high sugar levels produced by diabetes.

Hyperglycemia in people with diabetes causes these endothelial cells to generate toxic molecules known as reactive oxygen species (ROS).

Researchers found paroxetine prevents hyperglycemia-initiated ROS damage to endothelial cells in two ways. The first way is that it directly reduces concentrations of superoxide. The second is that it suppresses superoxide production by mitochondria.

In a hyperglycemic environment, mitochondria are cells’ biggest source of superoxide. According to the researchers, paroxetine inhibits this activity without interfering with the mitochondria’s vital normal function.

More experiments yielded additional evidence that paroxetine protects endothelial cells under hyperglycemic conditions. Reactive oxygen species cause significant damage to DNA, RNA and proteins. However, cell-culture experiments show paroxetine significantly reduced this effect.

The drug showed similar results when tested on rat "aortic rings," which are small pieces of blood vessel kept alive with tissue-culture techniques. When treated with the vasodilator acetylcholine, these rings dilated as if they were still part of a functioning circulatory system.

The team tested paroxetine in rats that had been injected with streptozotocin, which is a chemical that induces diabetes. The animals given paroxetine developed hypoglycemia, but their arteries retained the ability to dilate.

"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 in a statement. "We’ll need to carefully characterize its safety profile in diabetic patients, but I think there’s definite potential here."

Diabetes, online Dec 12, 2012