title: The histamine H3 receptor: an attractive target for the treatment of cognitive disorders.
abstract: The histamine H3 receptor, first described in 1983 as a histamine autoreceptor and later shown to also function as a heteroreceptor that regulates the release of other neurotransmitters, has been the focus of research by numerous laboratories as it represents an attractive drug target for a number of indications including cognition. The purpose of this review is to acquaint the reader with the current understanding of H3 receptor localization and function as a modulator of neurotransmitter release and its effects on cognitive processes, as well as to provide an update on selected H3 antagonists in various states of preclinical and clinical advancement. Blockade of centrally localized H3 receptors by selective H3 receptor antagonists has been shown to enhance the release of neurotransmitters such as histamine, ACh, dopamine and norepinephrine, among others, which play important roles in cognitive processes. The cognitive-enhancing effects of H3 antagonists across multiple cognitive domains in a wide number of preclinical cognition models also bolster confidence in this therapeutic approach for the treatment of attention deficit hyperactivity disorder, Alzheimer's disease and schizophrenia. However, although a number of clinical studies examining the efficacy of H3 receptor antagonists for a variety of cognitive disorders are currently underway, no clinical proof of concept for an H3 receptor antagonist has been reported to date. The discovery of effective H3 antagonists as therapeutic agents for the novel treatment of cognitive disorders will only be accomplished through continued research efforts that further our insights into the functions of the H3 receptor.
authors.affiliation: Division of Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. tim.esbenshade@abbott.com
authors.forename: T A
authors.initials: TA
authors.lastname: Esbenshade
authors.forename: K E
authors.initials: KE
authors.lastname: Browman
authors.forename: R S
authors.initials: RS
authors.lastname: Bitner
authors.forename: M
authors.initials: M
authors.lastname: Strakhova
authors.forename: M D
authors.initials: MD
authors.lastname: Cowart
authors.forename: J D
authors.initials: JD
authors.lastname: Brioni
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy*; D006632:Histamine / Q000502:physiology; D054828:Histamine H3 Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008568:Memory / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D054828:Histamine H3 Antagonists; D018377:Neurotransmitter Agents; D018100:Receptors, Histamine H3; D006632:Histamine