Formation of highly analgesic morphine-6-glucuronide following physiologic concentration of morphine in human brain.
3H-Morphine at physiologic concentration was metabolized in vitro to its 3- and 6-glucuronides by human brain homogenate. Recombinant UGT2B7, one of the UDP-glucuronosyltransferase (UGT) isoforms, is able to glucuronidate the 3- and 6-hydroxy groups of morphine at nanomolar concentrations. These results suggest that endogenous morphine is converted to its 6-glucuronide, a more highly analgesic substance than the parent compound, to suppress effectively pain symptoms in humans.
Yamada
Hideyuki
H
Laboratory of Molecular Life Science, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Ishii
Kumiko
K
Ishii
Yuji
Y
Ieiri
Ichiro
I
Nishio
Syunji
S
Morioka
Takato
T
Oguri
Kazuta
K
D000701:Analgesics, Opioid / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004827:Epilepsy / Q000601:surgery; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009020:Morphine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009022:Morphine Derivatives / Q000032:analysis / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism*; D014316:Tritium
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D018847:Opioid Peptides; D014316:Tritium; C035349:morphine-6-glucuronide; D009020:Morphine; D014453:Glucuronosyltransferase