Creating a free account will enable you to subscribe to our daily and weekly email newsletters, as well as customize your reading experience to show only the categories most relevant to you.
Signing up only take a few minutes, so why not give it a try and see what you've been missing out on.
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have described a pair of drug candidates that advance the search for new treatments for pain, addiction and other disorders.
The two new drug scaffolds, described in a recent edition of The Journal of Biological Chemistry, offer researchers novel tools that act on a demonstrated therapeutic target, the kappa opioid receptor (KOR), which is located on nerve cells and plays a role in the release of the neurotransmitter dopamine. While compounds that activate KOR are associated with positive therapeutic effects, they often also recruit a molecule known as βarrestin2 (beta arrestin), which is associated with depressed mood and severely limits any therapeutic potential.
"Compounds that act at kappa receptors may provide a means for treating addiction and for treating pain; however, there is the potential for the development of depression or dysphoria associated with this receptor target," said Laura Bohn, a TSRI associate professor who led the study. "There is evidence that the negative feelings caused by kappa receptor drugs may be, in part, due to receptor actions through proteins called beta arrestins. Developing compounds that activate the receptors without recruiting beta arrestin function may serve as a means to improve the therapeutic potential and limit side effects."
The new compounds are called "biased agonists," activating the receptor without engaging the beta arrestins.
Research Associate Lei Zhou, first author of the study with Research Associate Kimberly M. Lovell, added, "The importance of these biased agonists is that we can manipulate the activation of one particular signaling cascade that produces analgesia, but not the other one that could lead to dysphoria or depression."
The researchers note that the avoidance of depression is particularly important in addiction treatment, where depressed mood can play a role in relapse.
The two drug candidates also have a high affinity and selectivity for KOR over other opioid receptors and are able to pass through the blood-brain barrier. Given these promising attributes, the scientists plan to continue developing the compounds.
In addition to Bohn, Lovell and Zhou, other authors of the study, Development of Functionally Selective, Small Molecule Agonists at Kappa Opioid Receptors include Angela M. Phillips, John M. Streicher, Edward Stahl, Cullen L. Schmid, Michael D. Cameron, Peter Hodder and Franck Madoux of The Scripps Research Institute; the chemistry was led by Kevin J. Frankowski, Stephen R. Slauson, Thomas E. Prisinzano and Jeffrey Aubé of the University of Kansas.
This work was supported by the National Institutes of Health (grant R01 DA031927).
Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our Pain / Anesthetics category page for the latest news on this subject.
Please use one of the following formats to cite this article in your essay, paper or report:
Institute, Scripps Research. "Promising drug candidates, biased agonists, developed for pain and addiction." Medical News Today. MediLexicon, Intl., 16 Jan. 2014. Web.
17 Apr. 2014. <http://www.medicalnewstoday.com/releases/271194>
Institute, S. (2014, January 16). "Promising drug candidates, biased agonists, developed for pain and addiction." Medical News Today. Retrieved from
Please note: If no author information is provided, the source is cited instead.
If you write about specific medications, operations, or procedures please do not name healthcare professionals by name.
For any corrections of factual information, or to contact our editorial team, please use our feedback form. Please send any medical news or health news press releases to:
Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.
This page was printed from: http://www.medicalnewstoday.com/releases/271194.php
Visit www.medicalnewstoday.com for medical news and health news headlines posted throughout the day, every day.
© 2004-2014 All rights reserved. MNT (logo) is the registered trade mark of MediLexicon International Limited.