Systemic administrations: where does the drug go?

[Vieno]

I've recently learnt that certain receptors have as different as opposing effects in different parts of the brain. How can a systemically administrated drug work in any sensible way since it is supposed to go everywhere?

Let's use mu-opioid modulation as an example. Systemic administrations of opioids produce a lot of pleasure. Antagonists do not behave in opposite ways: naltrexone and naloxone do not significantly reduce the pleasure humans get from naturally rewarding stimuli. In some experiments they have reduced pleasure to some extent, but these findings are in the minority and generally it seems that if you take an opioid antagonist, you'll feel natural pleasure just as well as you used to. But here's some conflicting data: in recent microinjection studies, mu antagonism in certain spots of the brain was found to prevent natural pleasure: in some spots of the brain, mu AGONISM was found to reduce pleasure. I'm referring to this study: http://www.lsa.umich.edu/psych/research&labs/berridge/publications/preprints/smith%20mahler%20pecina%20&%20berridge%20-%20pleasure%20chapter%20proofs.doc.pdf


Don't the effects of systemically administrated mu agonists and mu antagonists now seem a bit odd? Why don't they induce any of the aforementioned effects that are specific to certain loci? Don't they go everywhere? Are there places they don't enter?

Generally, any info on the mechanisms of systemic administrations is appreciated - I'd like to better understand the topic.

Thank you!

 

[sekio]

The drugs distribute through diffusion to tissues that have an affinity for them. It's dependent on the polarity and structure of the molecvule as well as the affinity it has for e.g. serum protiens, membrane protiens and the like.

 

[Vieno]

Are you saying that it's possible that systemically administrated drugs do not get into all brain loci due to differences in the properties of the tissues of different loci?

Like, a drug crosses the BBB and enters most parts of the brain but can't get to some specific spot due to its tissue being different than in most parts of the brain?

 

[endotropic]

Are you saying that it's possible that systemically administrated drugs do not get into all brain loci due to differences in the properties of the tissues of different loci?

Like, a drug crosses the BBB and enters most parts of the brain but can't get to some specific spot due to its tissue being different than in most parts of the brain?

It is possible for a drug to reach higher concentrations in some parts of the brain than others, but it's very unlikely for a drug to enter the brain and be COMPLETELY excluded from some specific part. There's no real barrier between different areas of the brain like there is between the CNS and the rest of the body.

It's also very unlikely for the route of administration (e.g. through the skin vs. oral) to affect the tissue distribution, EXCEPT that the tissue you directly apply the drug to will see higher concentrations than the rest of the body, at least at first.