Nicotine Increases Codeine Analgesia Through the Induction of Brain CYP2D and Central Activation of Codeine to Morphine.

ABSTRACT: CYP2D metabolically activates codeine to morphine, which is required for codeine analgesia. Permeability across the blood-brain barrier, and active efflux, suggests that initial morphine in the brain after codeine is due to brain CYP2D metabolism. Human CYP2D is higher in the brains, but not in the livers, of smokers and 7-day nicotine treatment induces rat brain, but not hepatic, CYP2D. The role of nicotine-induced rat brain CYP2D in the central metabolic activation of peripherally administered codeine and resulting analgesia was investigated. Rats received 7-day nicotine (1 mg/kg subcutaneously) and/or a single propranolol (CYP2D mechanism-based inhibitor; 20 μg intracerebroventricularly) pretreatment, and then were tested for analgesia and drug levels following codeine (20 mg/kg intrape

SUBMITTER: McMillan DM 

PROVIDER: S-EPMC4916647 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature