Figure 1.

The analgesic time course following codeine and morphine suggests peripheral morphine levels do not predict central morphine levels or analgesia. Codeine (20 mg/kg) produced an analgesic peak around 15 min postinjection (T_MAX=13+1.8 min, mean+SEM; n=22; a). A morphine dose (3.5 mg/kg), chosen to match peak analgesia from codeine, resulted in an equivalent albeit later analgesia peak around 30 min postinjection (T_MAX=27+4.9 min; n=8). At 15 min postinjection, the time of the codeine analgesia peak, the morphine dose (n=10) produced similar plasma morphine levels to the codeine dose (n=5; b), and lower brain morphine levels (c) consistent with the lower analgesia. A between-animal study design was used; *p<0.05 compared with codeine (20 mg/kg) using an unpaired t-test.