Figure 5:

Selective inhibition of CYP2D in the brain with propranolol decreased brain oxymorphone/oxycodone ratio in males > females in estrus > females in diestrus.

Brain oxycodone (OC) and brain oxymorphone (OM) assessed by microdialysis after 7.5 mg/kg oral oxycodone (N=9/group) were used for the metabolite/parent ratio (brain OM/OC ratio), a phenotype measure for in vivo CYP2D in the brain; a, brain OM/OC-time curve in M (F_{Pre-treatment(1,127)} = 19.02, p<0.0001; F_Time(7,127) = 3.05, p=0.0053; F_{Interaction(7,127)} = 1.06, p=0.3962), in FE (F_{Pre-treatment(1,128)} = 2.67, p=0.1047; F_Time(7,128) = 3.69, p=0.0012; F_{Interaction(7,128)} = 0.52, p=0.8202), and in FDE (F_{Pre-treatment(1,126)} = 0.20, p=0.6565; F_Time(7,126) = 1.70, p=0.1155; F_{Interaction(7,126)} = 0.49, p=0.8432). b, brain OM/OC ratio AUC_0-105 (F_{Sex/Cycle(2,24)} = 2.77, p=0.0828; F_{Pre-treatment(1,24)} = 10.74, p=0.0032; F_{Interaction(2,24)} = 5.47, p=0.0110). c, 30-min analgesia correlated with brain OM/OC ratio AUC_0-105 (Spearman r=−0.3748, p=0.0057). Brain OM/OC-time curve was assessed using mixed ANOVA. Brain OM/OC ratio AUC_0-105 was assessed using two-way ANOVA repeated by pre-treatment; **p<0.01, relative to vehicle pre-treated FDE, and ^###p<0.001 relative to its respective vehicle using Bonferroni post-hoc analysis. Correlations were assessed using Spearman Correlation.