MadSci Network: Medicine
Query:

Re: Why doesn't Domperidone cross the Blood Brain Barrier?

Date: Fri Jul 20 16:06:15 2007
Posted By: david bell, Faculty, life & Envrionmental sciences, nottingham uni
Area of science: Medicine
ID: 1184944019.Me
Message:

Okay, let me make clear that this is a specialised question, that the BBB isn't my speciality, and I haven't spent that much time looking at this issue.

Caveats aside, the normal warning for high penetration across the BBB is lipophilicity, and domperidone has that. However, domperidone is also a substrate for P-glycoprotein. Hence, the theory would be that PGP causes rapid excretion of the compound from the BBB.
http://www.medscape.com/viewarticle/409741_4
domperidone lipophilicity here:
http://www.pnas.org/cgi/reprint/91/1/68.pdf

It seems there is a lot of literature on this, and I can't imagine you will have difficulty searching. There are pgp null mice, people have expressed the pgp in cells, and there are inhibitors of pgp available.

yours
david


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