Phenobarbital confers its diverse effects by activating the orphan nuclear receptor CAR

Susumu Kodama, Masahiko Negishi

Research output: Contribution to journalReview articlepeer-review

67 Citations (Scopus)


In the early 1960s, phenobarbital (PB) was shown to induce hepatic drug metabolism and the induction was implicated in the molecular mechanism of drug tolerance development. Since then, it has become evident that PB not only induces drug metabolism, but also triggers pleiotropic effects on liver function, such as cell growth and communication, proliferation of the endoplasmic reticulum, tumor promotion, glucose metabolism, steroid/ thyroid hormone metabolism, and bile acid synthesis. Upon activation by PB and numerous PB-type inducers, the nuclear receptor CAR mediates those pleiotropic actions by regulating various hepatic genes, utilizing multiple regulatory mechanisms.

Original languageEnglish
Pages (from-to)75-87
Number of pages13
JournalDrug Metabolism Reviews
Issue number1-2
Publication statusPublished - 2006
Externally publishedYes


  • CAR
  • Cytochrome P450
  • Gene transcription
  • Gluconeogenesis
  • Hepatic metabolism
  • Hepatocellular carcinoma
  • Liver
  • Nuclear receptors

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)


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