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 cells interior after activation. It is thought that the activated receptors 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.
Heidi Hardman | EurekAlert!
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A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
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