October 2, 2012
Common Anxiety Drug Has Benefits For Heart Failure Prevention
Lawrence LeBlond for redOrbit.com - Your Universe Online
People who suffer from depression and are on a common medication used to treat such conditions could have the added benefit of heart failure prevention, according to a new study from researchers at the University of Michigan.Researchers have found that the depression drug Paroxetine, a selective serotonin reuptake inhibitor (SSRI) commonly sold under the name Paxil, inhibits G protein-coupled receptor kinase 2 (GRK2), a protein that becomes over-expressed when people have heart failure. And although “off-target” effects are known with many commonly used drugs, the effects seen in Paroxetine are the first to identify a direct link between a specific SSRI and a protein target in the signal system.
The finding was made by research carried out by John Tesmer, professor at the UM Life Sciences Institute and professor in the Dept. of Pharmacology at the UM Medical School, and his associates. Results of the team´s findings are published electronically in the journal ACS Chemical Biology.
Kristoff Homan, a postdoctoral fellow in Tesmer's lab, said the discovery almost did not happen. “It was completely serendipitous.”
Before beginning a larger search for compounds that would inhibit GRK2, the team screened a small library of around 2,000 compounds that contains many FDA-approved drugs. Through a testing and screening procedure of these drugs, the researchers found that Paroxetine adheres to and inhibits the activity of GRK2.
GRK2 becomes increasingly expressed as the system that regulates normal heartbeat and the strength of the heart's contractions weakens. Paroxetine, the team found, improved the strength of the heart's contractions in an animal model without interfering with the heart rate.
Paroxetine has been successfully used as an SSRI for 30 years, but Tesmer said at the currently prescribed doses it probably doesn´t inhibit GRK2 enough to be used for heart failure.
However, if modifications to the chemical structure of paroxetine that improve potency while decreasing SSRI activity can be identified, the team hopes to start the process of optimization and to develop these compounds into therapeutic leads within the next several years, added Homan.