Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Opiate cocktail may spare cells from morphine’s dark side

07.06.2005


Although morphine is well known as a highly effective analgesic, its clinical utility is severely limited by the development of drug tolerance, the requirement for increasing doses to maintain analgesic effect, and the development of physical dependence. In the June 7 issue of Current Biology, researchers report a new study showing that the administration of a drug cocktail containing morphine along with small doses of two versions of methadone, a related opioid drug, significantly reduced both tolerance and dependence in test animals.



The work is reported by Li He and Jennifer Whistler of the Ernest Gallo Clinic and Research Center and the University of California, San Francisco.

The analgesic effects of morphine arise through the interaction of the drug with a specialized protein on the surface of cells, the mu opioid peptide receptor, or "MOP" receptor. MOP receptors are also activated by other opioid drugs and by endogenous opioids, such as endorphins. However, morphine is unique in that unlike other opioids, it does not cause the MOP receptor to be internalized into the cell’s interior after activation. It is thought that the activated receptor’s persistence at the cell surface leads to a compensatory overactivation of a particular signaling pathway in the cell--a signaling imbalance that is a hallmark of opiate tolerance and dependence. This suggests that the promotion of MOP-receptor internalization might prevent such cellular signaling imbalances, and indeed past work from Whistler indicated that mutant versions of the receptor that are more readily internalized were associated with reduced levels of morphine tolerance in mice.


In the new work, the researchers sought a more clinically practical approach to facilitating MOP-receptor internalization in the presence of morphine. Reasoning that because other opioid drugs promote internalization of MOP receptors, and that their presence in combination with morphine may prevent the persistence of activated MOP receptors at the cell surface, the authors developed a drug cocktail containing morphine along with two chemical versions of the opioid methadone, which is tolerated, with limited side effects, at low doses.

The authors indeed found that the combination of morphine with the methadone mixture prevented the activation of cellular signaling pathways associated with morphine tolerance and dependence. They also showed, perhaps most importantly, that whereas rats receiving only morphine develop tolerance to the drug, those rats receiving the morphine/methadone cocktail did not show tolerance. Moreover, past work has not indicated whether the promotion of MOP-receptor internalization could prevent the development of morphine dependence, but in the new study, the authors discovered that rats receiving the morphine/methadone cocktail also experienced reduced morphine dependence.

In light of their findings, the authors propose that an opiate cocktail that combines morphine with small doses of methadone would increase the effectiveness of morphine for the treatment of chronic pain.

Heidi Hardman | EurekAlert!
Further information:
http://www.cell.com

More articles from Studies and Analyses:

nachricht Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

A novel synthetic antibody enables conditional “protein knockdown” in vertebrates

20.08.2018 | Life Sciences

Metamolds: Molding a mold

20.08.2018 | Information Technology

It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

20.08.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>