WASHINGTON, Oct 2:
A common drug used to treat depression and anxiety has the potential to prevent heart failure, a new study has claimed.
Researchers led by professor John Tesmer, at the University of Michigan, found that Paroxetine inhibits G protein-coupled receptor kinase 2 (GRK2), a protein kinase that becomes over-expressed when people have heart failure.
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) sold under the name Paxil.
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, said Kristoff Homan, a postdoctoral fellow in Tesmer’s lab.
The discovery almost did not happen. “It was completely serendipitous,” Homan said in a statement.
Researchers screened a small library of 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.
However, 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.
The finding was published in the journal ‘ACS Chemical Biology’. (PTI)
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