Effect of CYP2 inhibition on the efficacy of CNS-acting substrates. Inhibiting the specific activity of CYP2 enzymes in the brain can influence the behavioral response to CNS-acting substrates. (A) CYP2B inhibition by the CYP2B MBI C8-xanthate (C8-X) in the brain increased propofol-induced sleep times in rats. (B) Inducing CYP2B in the brain by 7 days of nicotine treatment reduced propofol-induced sleep times, and this effect was reversed when rats were given C8-X. (C) CYP2D inhibition by the CYP2D MBI propranolol (PL) in the brain reduced analgesia at early time points after administration of its substrate codeine, but had no effect at later time points when morphine made peripherally enters the brain. (D) CYP2D inhibition by propranolol in the brain after a morphine injection did not have an effect on analgesia at any time; morphine is not a substrate for CYP2D. Data compiled from previously published reports (Khokhar and Tyndale, 2011; Zhou et al., 2013). *P < 0.05. ACSF, artificial cerebrospinal fluid; %MPE, percent maximal possible effect; SC, subcutaneous.