Targeting drugs to reduce side effects

by Rosie Hales

(Medical Xpress)—Consider ice cream – the base of which is frozen cream. Ingredients are then added to make different flavours. All these flavours are distinctly different but are created from the same foundation.

The same goes for actions of phosphodiesterases or PDEs – enzymes that are key targets for drugs that combat various cardiovascular and .

Although PDEs carry out only one reaction in cells, they inactivate small signaling molecules. As humans, we can create about 120 different "flavours" of PDEs, using the 26 different PDE genes in our genome.

After conducting a review of the drugs that act by targeting individual PDE "flavours", Donald Maurice, Director of the Cardiac, Circulatory and Respiratory Research Program at Queen's, and his international co-authors have learned that many of the drugs' side effects can be avoided.

When PDEs are inhibited, there is an increase in the rhythmic beating of the heart and blood pressure is often reduced. Common PDE-inhibiting drugs include caffeine and Viagra.

The research review aimed to study previous research on PDE's in order to position past results in the context of the recently discovered "flavours" of PDEs, which can be targeted individually by .

"Few PDE drugs currently available have the selectivity needed to target the individual PDE "flavours" that contribute to human diseases," says Dr. Maurice, also a professor in the Department of Biomedical and Molecular Sciences. "Yes, it's important to understand successes, but comprehensive critical reviews give researchers the chance to understand the basis of failures and make improvements."

While PDE-inhibitors have been used in the past to treat cardiovascular illnesses, this review outlines recent advances from the laboratories of the authors that have led to an increased interest in the design of PDE-acting drugs for conditions such as Alzheimer's, schizophrenia and diabetes.

The review also found that drugs that target specific locations within a cell are more likely to be successful.

"If you can regulate individual events happening in individual locations of the cell then you can leave the normal functions of the cell unaffected while challenging the abnormal ones," says Dr. Maurice.

Dr. Maurice's was published in Nature Reviews Drug Discovery. His research program is funded by the Canadian Institutes of Health Research.

More information: "Advances in targeting cyclic nucleotide phosphodiesterases." Donald H. Maurice, Hengming Ke, Faiyaz Ahmad, Yousheng Wang, Jay Chung & Vincent C. Manganiello. Nature Reviews Drug Discovery 13, 290–314 (2014) DOI: 10.1038/nrd4228
Published online 01 April 2014

Related Stories

New study examines hearing loss, Viagra use

date May 18, 2010

Research by a University of Alabama at Birmingham (UAB) professor shows an association between hearing loss and the use of the erectile dysfunction drug Viagra.

Viagra relatives may shrink abnormally large hearts

date Sep 24, 2009

Compounds related to Viagra, which is already in clinical trials to prevent heart failure, may also counter the disease in a different way, according to a study published online today in the journal Circulation Research. The re ...

Recommended for you

Rising antibiotic shortages raise concerns about patient care

date Apr 23, 2015

Shortages of key antibiotics, including gold-standard therapies and drugs used to treat highly resistant infections, are on the rise, according to a new study of shortages from 2001 to 2013 published in Clinical Infectious Di ...

Study supports HPV vaccination guidelines

date Apr 21, 2015

(HealthDay)—New research finds that young women who get the HPV vaccine gain significant protection against infection in three parts of the body if they haven't already been exposed to the human papillomavirus.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.