Nuclear receptors (NRs) belong to a family of ligand-dependent transcription factors. The target genes of NRs include many drug metabolizing enzymes and transporters. The central nervous system (CNS) bears the expression of NRs, drug metabolizing enzymes and transporters. NRs that express in the brain can be divided into three groups according to their characteristics of ligand binding: steroid hormone receptors, non-steroid hormone receptors, and orphan receptors. The NR-mediated regulation of drug metabolizing enzymes and transporters plays important roles in the metabolism and disposition of drugs in the CNS and the penetration of endogenous and exogenous substances through the blood-brain barrier (BBB). NR-mediated regulation of drug metabolizing enzymes and transporters can cause the toxicological effects of xenobiotics in the CNS and also lead to drug resistance in the centrum. The regulatory pathways of drug metabolizing enzymes and transporters can provide new strategies for selective regulation of the BBB permeability and drug metabolism in the brain. This review focuses on the importance of NR-mediated regulation of drug metabolizing enzymes and transporters in the CNS and the implications of this regulation in the therapeutic effect of CNS drugs and CNS side effects of drugs and other xenotoxicants.
Keywords: Nuclear receptors; blood–brain barrier; central nervous system; cytochrome P450; drug transporters.