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:5/26/2016)... ... 26, 2016 , ... Catalent Pharma Solutions, the leading global ... and global clinical supply services, today announced two key appointments and the opening ... and strategic growth plans in the Asia Pacific region. , Howard Kim has ...
(Date:5/26/2016)... CA (PRWEB) , ... May 26, 2016 , ... In an effort to provide hair ... available to both Snapchat users and those who do not use the app. Dr. Mohebi, ... his new page, Dr. Mohebi Live . , Dr. Mohebi says, “The positive ...
(Date:5/26/2016)... ... May 26, 2016 , ... ... for eating disorders, is opening a brand new child and adolescent residential treatment ... and their families with even more specialized eating disorder treatment and access to ...
(Date:5/26/2016)... ... May 26, 2016 , ... ... multitude of activities from daily practices, arts & crafts, discussions, and games all ... East-D’Anna and Christy Evans have combined backgrounds in kids’ yoga, collegiate sport yoga ...
(Date:5/26/2016)... ... May 26, 2016 , ... Eugene Batelli, ... Along with his wonderful accolades and stellar patient reviews, Dr. Batelli continues to ... , Dr. Eugene Batelli is a highly trained Podiatric Surgeon who specializes in ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... , May 25,2016 FDA ... near-infrared Cellvizio platform for urological and surgical applications ... MKEAY) inventor of Cellvizio®, the multidisciplinary confocal laser ... milestone in the US with the 12 th ... Drug Administration (FDA). This new FDA clearance covers ...
(Date:5/25/2016)... , Germany and GERMANTOWN, ... QIAGEN N.V. (NASDAQ: QGEN ; Frankfurt Prime Standard: ... licensing and co-development agreement with Therawis Diagnostics GmbH to develop ... be to develop and market PITX2 as a marker to ... high-risk breast cancer patients. "We are pleased to ...
(Date:5/25/2016)... According to market research "Global ... Demand Forecast to 2022 - Industry Insights by Type ... by P&S Market Research, the global insulin delivery device ... it is expected to grow at a CAGR of ... segment is expected to witness the fastest growth at ...
Breaking Medicine Technology: