Posted by BrittPark on November 5, 2002, at 15:20:02
In reply to Reply to Britt, posted by Kara Lynne on November 5, 2002, at 14:15:42
It's still unknown how tolerance to opioids develops. It was only discovered recently, for example, that exogenous opiates like morphine caused clustering of opioid receptors, but blocked endocytosis of the clusters. The addition of a compound that causes the clusters to be endocytized actually blocks tolerance development. It used to be believed that cellular uptake of opioids was necessary for tolerance development-- exactly the opposite of what's been found.
I believe part of the mechanism for opioid tolerance is simple down-regulation of opioid receptors. There is no physical reason that some people don't down regulate when challenged, perhaps because they already have something biologically amiss that causes opioid receptors to be up-regulated or desensitized. There could also be a genetic component. This has been found to be true for alcohol (which by the way affects the opioid system). I imagine there's a genetic component to cocaine addiction too, since some people are completely take-it-or-leave it and others become addicted within 2-3 exposures.Take a look at my other post about opioid agonist / low dose antagonist drug development.
Cheers,
Britt
poster:BrittPark
thread:126471
URL: http://www.dr-bob.org/babble/20021101/msgs/126544.html