6.
Molecular modelling analysis of the metabolism of morphine
Fazlul Huq
School of Biomedical Sciences,
Faculty of Health Sciences, The University of Sydney
E-mail :
f.huq@fhs.usyd.edu.au.
Abstract:
Molecular modelling analyses based on
molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G*
level) calculations show that morphine and its metabolites have
similar LUMO-HOMO energy differences except MN which has a much lower
value indicating its greater kinetic lability. The greater kinetic
lability of morphinone and its binding with sulfur-containing
antioxidants glutathione, metalothionein and cysteine and the
resulting alteration of the antioxidant status of the cell explain why
the metabolite is much more toxic than morphine itself. The presence
of multiple charged and neutral regions on the surface of morphine and
M6G can be seen to support the idea of their multiple sites
interaction with opioid receptors.
Key words:
Morphine, cancer, palliative care, morphinone, toxicity, molecular
modelling
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