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 selective serotonin reuptake inhibitor (SSRI) sold under the name Paxil, inhibits G protein-coupled receptor kinase 2 (GRK2), a protein kinase that becomes over-expressed when people have heart failure.
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 Chemical Biology.
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/a… 21/cb3003013
Journal reference: ACS Chemical Biology
Provided by University of Michigan
- Molecule involved in heart failure now implicated in heart attack damage Sep 15, 2010 | not rated yet | 0
- Inhibition of GRK2 is protective against acute cardiac stress injuries Nov 17, 2009 | not rated yet | 0
- Targeting flight-or-fight hormone response to combat heart failure Jun 24, 2010 | not rated yet | 0
- Are older antidepressants better for depression in Parkinson's disease? Dec 17, 2008 | not rated yet | 0
- Link Between Antidepressants and Birth Defect Sep 29, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
21 hours ago From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
Europe's medicines watchdog said Friday the benefits of acne drug Diane-35, also widely used as a contraceptive, outweigh the risk of developing blood clots in the veins—when correctly prescribed.
Medications May 17, 2013 | not rated yet | 0
Singapore's Agency for Science, Technology and Research (A*STAR) and Switzerland's Cytos Biotechnology AG today announced that the first healthy volunteer has been dosed in a Phase 1 clinical trial with their ...
Medications May 17, 2013 | 5 / 5 (1) | 0
(Medical Xpress)—An aspirin a day may not always keep heart disease away, say two University of Florida cardiologists. But a new algorithm they have developed outlines factors physicians should weigh as ...
Medications May 16, 2013 | 3.5 / 5 (2) | 0 |
(HealthDay)—The U.S. Food and Drug Administration has approved new, lower-dose labeling for the popular sleep drug Ambien (zolpidem) in an effort to cut down on daytime drowsiness that could be a hazard ...
Medications May 15, 2013 | not rated yet | 0
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
13 hours ago | not rated yet | 0 |
The latest makeover to a massive psychiatric tome honored by some, reviled by others and even called the "Bible" of mental disorders is being released Saturday with a host of new changes.
11 hours ago | not rated yet | 0
A new case of the deadly coronavirus has been detected in Saudi Arabia where 15 people have already died after contracting it, the health ministry announced on Saturday on its Internet website.
11 hours ago | not rated yet | 0
22 hours ago | 5 / 5 (1) | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
23 hours ago | 5 / 5 (1) | 0 |
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
13 hours ago | 5 / 5 (2) | 0