Biochemistry

Pain Relief

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Science  02 Apr 2010:
Vol. 328, Issue 5974, pp. 19
DOI: 10.1126/science.328.5974.19-c
CREDIT: ISTOCKPHOTO.COM

The endogenous alkaloids of the opium poppy, such as morphine and codeine, have been used as analgesics for several millennia. These compounds and their precursors, especially thebaine, have also been used as the starting material for making semisynthetic opioids, with the aim of creating a less dangerous yet still potent drug. The focal differences are situated at positions C3 and C6: thebaine contains two O-methyl groups, codeine has undergone 6-O-demethylation, and morphine has been denuded of both O-methyl groups. Hagel and Facchini have identified the enzymes responsible for these reactions, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM), by differential transcript screening against a poppy varietal that is deficient in both morphine and codeine. Both enzymes are members of the α-ketoglutarate/Fe(II)–dependent dioxygenase family, and the mechanism probably involves the insertion of an oxygen into a C-H bond of the methyl group and then elimination of a molecule of formaldehyde.

Nat. Chem. Biol. 6, 273 (2010).

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