Abstract
The chemical structures of morphine and its metabolites are closely related to the clinical effects of drugs (analgesia and side-effects) and to their capability to cross the Blood Brain Barrier (BBB). Morphine-6-glucuronide (M6G) and Morphine-3-glucuronide (M3G) are both highly hydrophilic, but only M6G can penetrate the BBB; accordingly, M6G is considered a more attractive analgesic than the parent drug and the M3G. Several hypotheses have been made to explain these differences. In this review we will discuss recent advances in the field, considering brain disposition of M6G, UDP-glucoronosyltransferases (UGT) involved in morphine metabolism, UGT interindividual variability and transport proteins.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Analgesics, Opioid / chemistry
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Analgesics, Opioid / pharmacokinetics
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Animals
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Biological Transport
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Blood-Brain Barrier / metabolism*
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Brain / metabolism
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Glucuronosyltransferase / genetics
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Glucuronosyltransferase / metabolism
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Humans
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Liver / metabolism
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Mice
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Morphine / chemistry
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Morphine / pharmacokinetics*
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Morphine Derivatives / chemistry
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Morphine Derivatives / pharmacokinetics*
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Neoplasms / drug therapy
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Pain / drug therapy
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Pain / genetics
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Pain / metabolism
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Rats
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Receptors, Opioid, mu / genetics
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Receptors, Opioid, mu / metabolism
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Analgesics, Opioid
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Morphine Derivatives
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OPRM1 protein, human
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Receptors, Opioid, mu
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morphine-6-glucuronide
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Morphine
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UGT2B7 protein, human
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Glucuronosyltransferase
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morphine-3-glucuronide