The physiological and pathophysiological roles of neuronal histamine: An insight from human positron emission tomography studies

Research output: Contribution to journalReview articlepeer-review

153 Citations (Scopus)


Histamine neurons are exclusively located in the posterior hypothalamus, and project their fibers to almost all regions of the human brain. Although a significant amount of research has been done to clarify the functions of the histaminergic neuron system in animals, a few studies have been reported on the roles of this system in the human brain. In past studies, we have been able to clarify some of the functions of histamine neurons using different methods, such as histamine-related gene knockout mice or human positron emission tomography (PET). The histaminergic neuron system is known to modulate wakefulness, the sleep-wake cycle, appetite control, learning, memory and emotion. Accordingly we have proposed that histamine neurons have a dual effect on the CNS, with both stimulatory and suppressive actions. As a stimulator, neuronal histamine is one of the most important systems that stimulate and maintain wakefulness. Brain histamine also functions as a suppressor in bioprotection against various noxious and unfavorable stimuli of convulsion, drug sensitization, denervation supersensitivity, ischemic lesions and stress susceptibility. This review summarizes our works on the functions of histamine neurons using human PET studies, including the development of radiolabeled tracers for histamine H1 receptors (H1R: 11C-doxepin and 11C-pyrilamine), PET measurements of H1R in depression, schizophrenia, and Alzheimer's disease (AD), and studies on the sedative effects of antihistamines using H215O and H1R occupancy in the human brain. These molecular and functional PET studies in humans are useful for drug development in this millennium.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalPharmacology and Therapeutics
Issue number1
Publication statusPublished - 2007 Jan


  • Alzheimer's disease
  • Antihistamines
  • Brain
  • Depression
  • Histamine
  • Histamine neurons
  • PET
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


Dive into the research topics of 'The physiological and pathophysiological roles of neuronal histamine: An insight from human positron emission tomography studies'. Together they form a unique fingerprint.

Cite this