FIGURE 3.
Effect of CYP3A inhibition on mitragynine and 7‐OH mitragynine induced respiratory depression: (a,b) Mitragynine (5.5 mg·kg−1) induced significant respiratory depression in mice pretreated with vehicle (veh) but not in mice pretreated with ketoconazole (keto) (50 mg·kg−1, 30 min), (c, d) 7‐OH mitragynine (1.9 mg·kg−1) induced significant respiratory depression in vehicle and ketoconazole (50 mg·kg−1) pretreated mice. Ketoconazole pretreatment significantly reduced overall respiratory depression induced by mitragynine (e) but not that induced by 7‐OH mitragynine (f). N = 6 for all groups. All drugs administered by oral gavage dosing. In (a) ‐ (d), * P < 0.05, significantly different from vehicle control or as indicated; two‐way ANOVA with Dunnett's multiple comparisons. In (e) and (f), * P < 0.05, significantly different; ns, not significantly different, as indicated; 2 × 2 factorial by two‐way ANOVA with Bonferroni's multiple comparisons. See Table S1 for full test statistics