Histamine receptors in the CNS as targets for therapeutic intervention

Trends Pharmacol Sci. 2011 Apr;32(4):242-9. doi: 10.1016/j.tips.2011.01.003. Epub 2011 Feb 15.


Histamine has long been known to trigger allergic reactions and gastric acid secretion. However, it was later discovered that, in the brain, histamine regulates basic homeostatic and higher functions, including cognition, arousal, circadian and feeding rhythms. The sole source of brain histamine is neurons localized in the hypothalamic tuberomammillary nuclei. These neurons project axons to the whole brain, are organized into functionally distinct circuits influencing different brain regions and display selective control mechanisms. Although all histamine receptors (H1R, H2R, H3R and H4R) are expressed in the brain, only the H3R has become a drug target for the treatment of neurologic and psychiatric disorders, such as sleep disturbances and cognitive deficits. In this review, we discuss recent developments in the pharmacological manipulation of H3Rs and the implications for H3R-related therapies for neurological and psychiatric disorders. The legacy of Sir James Black.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Drug Delivery Systems
  • Humans
  • Mental Disorders / drug therapy*
  • Mental Disorders / physiopathology
  • Nervous System Diseases / drug therapy*
  • Nervous System Diseases / physiopathology
  • Receptors, Histamine / drug effects
  • Receptors, Histamine / metabolism
  • Receptors, Histamine H3 / drug effects*
  • Receptors, Histamine H3 / metabolism


  • Receptors, Histamine
  • Receptors, Histamine H3