The histamine H sub(3) receptor: an attractive target for the treatment of cognitive disorders

• Published in: British journal of pharmacology 2008-07, Vol.154 (6), p.1166-1181
• Main Authors: Esbenshade, T A, Browman, KE, Bitner, R S, Strakhova, M, Cowart, MD, Brioni, J D
• Format: Article
• Language: English
• ISSN: 0007-1188
• DOI: 10.1038/bjp.2008.147

The histamine H sub(3) 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 H sub(3) 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 H sub(3) antagonists in various states of preclinical and clinical advancement. Blockade of centrally localized H sub(3) receptors by selective H sub(3) 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 H sub(3) 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 H sub(3) receptor antagonists for a variety of cognitive disorders are currently underway, no clinical proof of concept for an H sub(3) receptor antagonist has been reported to date. The discovery of effective H sub(3) 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 H sub(3) receptor.