Sex differences in the antinociceptive effect of codeine and its peripheral but not central metabolism in adult mice.

Codeine is a natural opiate extracted from opium poppy (Papaver somniferum) and used to alleviate mild to moderate pain. The analgesic effect of this molecule results from its metabolism into morphine which is an agonist of the mu opioid receptor. Morphine's major metabolite morphine-3-glucuronide induces both thermal and mechanical hypersensitivies while codeine-6-glucuronide has been proposed to be antinociceptive.

Morphine-3-Glucuronide, Physiology and Behavior.

Morphine remains the gold standard painkiller available to date to relieve severe pain. Morphine metabolism leads to the production of two predominant metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). This metabolism involves uridine 5'-diphospho-glucuronosyltransferases (UGTs), which catalyze the addition of a glucuronide moiety onto the C3 or C6 position of morphine.