By
the A.M. Costa Rica wire services
Scientists are working to develop medicines that
have the pain-relieving effects of opioids without
the high risk of misuse and addiction.
Since misuse is linked to the euphoric effects of
the drug, investigators led by scientists at
National Institute on Drug Abuse, NIDA, intramural
labs are studying methadone, a drug used to manage
opioid addiction that does not have euphoric
effects as strong as many other opioids.
Animal studies show that mu opioid receptors in
the brain play a key role in the reinforcing
effects of opioid drugs, whereas the neuropeptide
galanin counteracts the effects of mu opioid
receptors.
In a recently published study, investigators found
a significant difference in the mechanisms of
action between methadone and morphine that is
determined by the activation of opioid receptor
complexes (heteromers) composed of both mu-opioid
receptors and one of the galanin receptor
subtypes; differences that are key to their
subsequent effects on the brain’s dopamine system.
The investigators found that the opioid-galanin
receptor heteromers determine the different
effects of methadone as compared to morphine and
fentanyl, showing methadone with a weaker ability
to activate the dopaminergic system linked to the
euphoric effects of opioids.
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These results should advance the search for
opioids less likely to attach to opioid-galanin
receptor heteromers, exemplified by methadone.
This finding also enables the search for compounds
that activate galanin receptors, which would be
expected to reduce the abuse liability of opioids.
The research was done by scientists at NIDA’s
intramural labs in Baltimore, the University of
Maryland, Harvard Medical School, and the
University of Barcelona.
Full article published in Journal of Clinical
Investigation may be reached at www.jci.org
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