GlaxoSmithKline's ($GSK) commonly used but historically slightly troubled antidepressant paroxetine (Seroxat or Paxil) could have a new life as a treatment for diabetic vascular complications, according to preclinical results coming out of the University of Texas Medical Branch (UTMB) at Galveston.
The team used endothelial cells, the cells that line the blood vessels, that had been exposed to high levels of glucose to screen a large database of 6,766 known drugs and experimental compounds. The aim was to pick out the agents that could stop the formation of hyperglycemia-induced reactive oxygen species (ROS), which damage the inside of the blood vessels (diabetic endothelial dysfunction) and lead to problems such as heart attacks, strokes, retinopathy, nephropathy and neuropathy.
One drug that they picked out, somewhat to their surprise, was paroxetine, which hasn't been studied in diabetes before.
"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," said UTMB professor Csaba Szabo in a press release.
In studies on the lab bench, the researchers found that paroxetine reduced the levels of the ROS superoxide and suppressed its production by mitochondria. It also cut the damage that ROS did to DNA, RNA and proteins. In rats with diabetes, paroxetine prevented damage to the rats' blood vessels.
Repurposing already-approved drugs can get useful therapeutics to the market more quickly because of the already-established safety data, as well as known formulation and manufacturing processes. Paroxetine has been linked with withdrawal, suicidal thoughts and violence, so careful safety studies and a close look at the dose will be needed, but if it is successful in clinical trials, paroxetine could fulfill an unmet need in a large new market.
- read the press release
- see the abstract
Editor's note: 'ROS superoxide dismutase' has been corrected to 'ROS superoxide'