Popular antidepressant might prevent heart failure

A medication usually used to help treat depression and anxiety disorders has the potential to help prevent heart failure, according to researchers at the University of Michigan.

John Tesmer, research professor at the U-M Life Sciences Institute and professor in the Department of Pharmacology at the U-M Medical School, and his research team at the Tesmer lab found that paroxetine, a (SSRI) sold under the name Paxil, inhibits G protein-coupled receptor kinase 2 (GRK2), a that becomes over-expressed when people have .

Although so-called "off target" effects are known for many commonly used drugs, this is the first report that identifies a direct link between a specific SSRI and a protein target in the signal system they study, said Kristoff Homan, a postdoctoral fellow in Tesmer's lab.

The paper, "Paroxetine is a Direct Inhibitor of G Protein-Coupled Receptor Kinase 2 and Increases Myocardial Contractility," was published electronically ahead of print on Aug. 21 in ACS .

The discovery almost did not happen. "It was completely serendipitous," Homan said.

Before beginning a larger search for compounds that would inhibit GRK2, the researchers screened a small library of approximately 2,000 compounds that contains many FDA-approved drugs as a test of their screening procedure—and found that paroxetine binds 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 is FDA-approved and has been clinically used as an SSRI for nearly 30 years, but at prescribed doses the compound probably does not inhibit GRK2 enough to be used for heart failure.

But if the researchers can identify modifications to the chemical structure of paroxetine that improve potency while decreasing SSRI activity, which Homan thinks they can do, the team hopes to start the process of optimization and to develop these compounds into therapeutic leads within the next several years, he said.

More information: pubs.acs.org/doi/abs/10.1021/cb3003013

Related Stories

Link Between Antidepressants and Birth Defect

Sep 29, 2009

(PhysOrg.com) -- Researchers in Denmark have studied almost half a million Danish children and found a slightly higher rate of septal heart abnormalities in babies whose mothers took an SSRI antidepressant ...

Recommended for you

WHO: Millions of Ebola vaccine doses ready in 2015

14 hours ago

The World Health Organization says millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines will start being tested in March.

Added benefit of vedolizumab is not proven

Oct 23, 2014

Vedolizumab (trade name Entyvio) has been approved since May 2014 for patients with moderately to severely active Crohn disease or ulcerative colitis. In an early benefit assessment pursuant to the Act on the Reform of the ...

Seaweed menace may yield new medicines

Oct 22, 2014

An invasive seaweed clogging up British coasts could be a blessing in disguise. University of Greenwich scientists have won a cash award to turn it into valuable compounds which can lead to new, life-saving drugs.

User comments