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Department of Medicine (D.W., W.M.P.), UCLA School of
Medicine;
College of Pharmacy (Y.-S.K.), Sookmyung Women's
University; and
Faculty of Medicine (U.B.), Philipps University
Marburg
The blood-brain barrier (BBB) permeability to morphine and
morphine-6-glucuronide (M6G) is measured under identical conditions using an intravenous injection method in the rat and HPLC separation of
morphine from its metabolites. The brain uptake of M6G expressed as
%ID/g was 32-fold lower than that of morphine, and the BBB permeability surface area product (PS) of M6G was 57-fold lower as
compared with that of morphine. Consistent with these in
vivo data, the 1-octanol/buffer partition study showed the
liposolubility of M6G was 187-fold lower than that of morphine. The CNS
origin of M6G analgesia after peripheral administration was confirmed because the analgesia was completely blocked by naloxone, which crosses
BBB, but not by naloxone methiodide, which does not enter brain from
blood. In conclusion, the BBB permeability to M6G is markedly reduced
as compared with morphine, consistent with the much lower lipid
solubility of M6G relative to morphine.
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