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- W1985361489 abstract "STKEAlthough morphine is highly effective against pain, long-term use is problematic because it leads to tolerance and dependence—both of which are likely associated with up-regulation of cAMP signaling and adaptive changes in the expression of target genes. Morphine analgesia and tolerance are mediated through the opioid peptide (MOP) receptor, which is also activated by endogenous opiates and methadone; however, unlike these other ligands, morphine does not stimulate endocytosis of the MOP receptor. He and Whistler found that a concentration of methadone that did not stimulate endocytosis by itself nevertheless resulted in MOP receptor endocytosis when administered with a saturating amount of morphine. The authors propose that joint occupation of a dimeric MOP receptor by morphine and methadone can engage the endocytic machinery with much reduced activation of the cAMP pathway. In rats, this mix inhibited the development of morphine tolerance (assessed by tail-flick) and dependence (assessed by the behavioral response to pharmacologically induced opiate withdrawal) without reducing the potency of morphine analgesia. — EMA Curr. Biol. 15 , 1028 (2005)." @default.
- W1985361489 created "2016-06-24" @default.
- W1985361489 date "2005-06-24" @default.
- W1985361489 modified "2023-09-26" @default.
- W1985361489 title "Reducing Tolerance and Dependence" @default.
- W1985361489 doi "https://doi.org/10.1126/science.308.5730.1845c" @default.
- W1985361489 hasPublicationYear "2005" @default.
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