Morphine, blood-brain barrier transport

Perhaps the most successful modification of the 4-phenylpiperidine derivatives of morphine is the 4-anilino compounds, such as fentanyl (3.15). This dmg is 50-100 times more active than morphine, owing mainly to its excellent transport across the blood-brain barrier and into the CNS as a result of its high lipophilicity. Spectacular activities ( 5000-6000 times that of morphine) have also been achieved by introducing ether or keto substituents (sufentanil), as in the meperidine or ketobemidone series. Fentanyl derivatives are very fast acting and of short duration. They are used in neuroleptanalgesia in surgery, in combination with neuroleptics or major tranquilizers like droperidol. 

After passage through the blood brain barrier, opioids have an anti-emetic effect (Blancquaert et al., 1986). Emesis inhibition is induced via blockade of an emesis centre located in a more central area of the formatio reticularis. This explains why the emetic effect of opioids is most apparent immediately after anministration, especially after rapid intravenous administration and is reduced or terminated when the compound has reached the CNS. The more hydrophilic opioids like morphine have stronger emetic side-effects than lipophilic compounds like methadone or fentanyl (Barnes et al., 1991), which are rapidly transported into the CNS. 

Bourasset E, Cisternino S, Temsamani J, Scher-rmann JM (2003) Evidence for an active transport of morphine-6-beta-D-glucuronide but not P-gly-coprotein-mediated at the blood-brain barrier. J Neurochemistry 86 1564-1567... 

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