Fig. 1.

Inhibition of CYP2 activity in the brain. Inhibiting activity of CYP2 enzymes specifically in the brain via MBI pretreatment can alter substrate and metabolite brain levels. (A) MBIs are substrates for their target enzymes, which are metabolized into intermediate compounds that bind irreversibly to the enzyme, thus inactivating it. MBIs are injected into the brain via i.c.v. injections. (B) Brain P450 inhibition increases the parent drug, illustrated for the active CYP2B substrate propofol: brain CYP2B inhibition by the i.c.v. MBI C8-xanthate (C8-X) increased propofol brain levels relative to vehicle [artificial cerebrospinal fluid (ACSF)] pretreatment; there was no difference in plasma propofol levels. (C) Brain P450 inhibition reduces metabolite levels, illustrated for the metabolically activated metabolite morphine from CYP2D substrate codeine: brain CYP2D inhibition by MBI propranolol (PL) pretreatment decreased morphine levels in the brain; there was no difference in plasma morphine levels (*P < 0.05). Data compiled from previously published reports (Khokhar and Tyndale, 2011; Zhou et al., 2013).