Navigation Links
Morphine dependency blocked by single genetic change
Date:1/28/2008

Morphines serious side effect as a pain killer its potential to create dependency has been almost completely eliminated in research with mice by genetically modifying a single trait on the surface of neurons. The study scientists think a drug can be developed to similarly block dependency.

The research was published online January 17 by Current Biology and appears in the journals January 23 print edition. The scientists were led by Jennifer Whistler, PhD, an investigator in the UCSF-affiliated Ernest Gallo Clinic and Research Center, and associate professor of neurology at UCSF.

Millions of people in the U.S. are given the opiate drug morphine for extreme pain caused by cancer, surgery, nerve damage and other conditions. It remains the pain killer of choice for many types of short-term pain, such as surgery, according to Whistler, but it is less useful for the treatment of chronic pain because its effectiveness decreases with continued use in a process called tolerance. As a consequence, an increasingly larger dose is required to treat the pain, thereby increasing the chance of addiction.

The bodys natural pain killers, such as endorphins, ease pain by first binding to receptors on the surface of neurons. The receptors cycle on and off like a light switch, Whistler says, regulating the intake of endorphin. This crucial control is absent when the neurons encounter morphine. The researchers strategy in their study was to try to trick neurons into responding to morphine in the more regulated way.

Strong evidence suggests that the natural on-off cycling occurs because the endorphin receptor withdraws from the cell surface, toward the cells interior, Whistler says. The migration from the cell surface is called endocytosis.

When the neuron receptors encounter morphine the light switch is broken, and the nervous system responds by becoming more tolerant of the drug, making the recipient more dependent on the drug.

To demonstrate their hunch that morphines unwanted effects were caused by the failure of its receptor to withdraw from the cell surface, the researchers genetically engineered mice with a single difference from normal mice: Receptors that encounter morphine in these mice can undergo endocytosis, as they normally do in the presence of endorphins. The researchers showed that with this single change, morphine remained an excellent pain killer without inducing tolerance and dependence.

As more pain medications are being removed from the market, new strategies to overcome chronic pain become crucial, Whistler says. If new opiate drugs can be developed with morphines pain killing properties but also with the ability to promote endocytosis, they could be less likely to cause the serious side effects of tolerance and dependence.

The research is the first direct demonstration that this single cellular change can block the bodys tendency to become tolerant of the drug, she points out.

Several strategies are now being tested to counter morphine addiction, Whistler says. These include development of morphine derivatives such as oxycontin, that are delivered in a time released manner or only once they have been processed in the digestive system. Other approaches seek to develop morphine derivatives that target only certain opioid receptors but not others.

The most promising aspect of these other approaches is that they have the potential to prevent or delay dependence and addiction to morphine, but few of them address the development of tolerance, Whistler said.


'/>"/>

Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

Related medicine news :

1. Morphine: a comfort measure for the dying or pain control for the living?
2. Blocking Potent Oxidant Could Prevent Morphine Tolerance
3. KV Pharmaceutical Announces FDA Approval for Morphine ER 100 mg and 200 mg Tablets
4. Morphine Painkillers Wont Impair Driving
5. Forever young: Differentiation blocked in tumor stem cells
6. New Device for Clearing Blocked Arteries in the Legs Receives FDA Clearance for Peripheral Use - Procedures Performed Across the US Within First 48 Hours
7. Novare Announces Completion of 100th Single Port Laparoscopic Procedure Using RealHand(R) High Dexterity (HD) Instruments
8. Pharmion and Methylgene Report Favorable Results for Phase 2 MGCD0103 Single- Agent Studies in Relapsed or Refractory Lymphomas at the 49th American Society of Hematology (ASH) Meeting
9. Transports Phase 2 Data Show Single Treatment SoloVir(TM) ETS Significantly Stops Progression of Cold Sore Episode
10. JRRD releases single-topic issue on traumatic brain injury and polytrauma
11. More women are choosing double mastectomy even when breast cancer is confined to a single breast
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/6/2016)... ... December 06, 2016 , ... METTLER TOLEDO has launched its ... including white papers, guides, handbooks, case studies, magazines, webinars, videos, catalogs, brochures, datasheets, ... 9,000 documents, webinars and videos available online, visit the METTLER TOLEDO Expertise ...
(Date:12/6/2016)... ... December 06, 2016 , ... ... 25th, when SevenPoint2 released the much-anticipated HydroFX for Water®. This first-of-its-kind water-soluble ... Featuring one of the world’s most powerful antioxidants, molecular hydrogen, HydroFX for ...
(Date:12/6/2016)... (PRWEB) , ... December 06, 2016 , ... Keeping Gift ... people choose gifts that are safe and age-appropriate for their recipients. This is the ... to reflect on the safety of items that would make good gifts for children. ...
(Date:12/6/2016)... Vancouver, B.C., Canada (PRWEB) , ... December 06, ... ... Consultants (STC) announce the availability of the newly updated International Audit Protocol Consortium ... world use IAPC EHS audit protocols to understand the scope of their EHS ...
(Date:12/6/2016)... ... 06, 2016 , ... The OSHA Training Center at ... Center headquartered in Northern California, has announced the addition of a Public Sector ... training to public sector employees. , “The primary goal of the Public Sector ...
Breaking Medicine News(10 mins):
(Date:12/5/2016)... 5, 2016 Research and Markets has ... (Instruments, Consumables), Application (Biomedical & Biochemical Research, Disease Diagnostics), End User ... to 2021" report to their offering. ... , , ... in 2021 from USD 574.8 Million in 2016, growing at a ...
(Date:12/5/2016)... 5, 2016 According to a new report published by ... - Global Opportunity Analysis and Industry Forecast, 2014 - 2022", the global surgical ... $5,255 million by 2022, growing at a CAGR of 6.4% from 2016 to ... share. Continue Reading ... ...
(Date:12/5/2016)... --  TrainerMD , the first HIPAA compliant software collaboration platform for ... Styku . Styku, a California -based ... users world-class, real-time 3D body scanning and analysis. Together with its ... hear and feel their health like never before. ... , , ...
Breaking Medicine Technology: