Abstract
The histaminergic system fulfills a major role in the maintenance of waking. Histaminergic neurons are located exclusively in the posterior hypothalamus from where they project to most areas of the central nervous system. The histamine H3 receptors are autoreceptors damping histamine synthesis, the firing frequency of histamine neurons, and the release of histamine from axonal varicosities. It is noteworthy that this action also extends to heteroreceptors on the axons of most other neurotransmitter systems, allowing a powerful control over multiple homeostatic functions. The particular properties and locations of histamine H3 receptors provide quite favorable attributes to make this a most promising target for pharmacological interventions of sleep and waking disorders associated with narcolepsy, Parkinson's disease, and other neuropsychiatric indications.
Footnotes
This work was supported by the European Community [Grant QLRT-2001-00826] (to H.L.H and J.-S.L.), the Deutsche Forschungsgemeinschaft [Grants SFB 575/3, SFB 575/8] (to H.L.H. and O.A.S.); and the Institut National de la Santé et Recherche Médicale (to J.-S.L).
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.170134.
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ABBREVIATIONS:
- REM
- rapid eye movement
- DREM
- direct transition from wake to REM sleep
- SWS
- slow wave sleep
- CNS
- central nervous system
- SKF91488
- 4-(N,N-dimethylamino)butylisothiourea
- BP2-94
- (R)-(−)-2-[[N-[1-(1H-imidazol-4-yl)-2-propyl]imino]phenylmethyl] phenol
- BF2.649
- 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine hydrochloride
- GSK-189254
- 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide
- JNJ-5207852
- 1-{3-[4-(piperidin-1-ylmethyl)phenoxy]propyl}piperidine
- ABT-239
- 4-(2-{2-[(2R)-2-methylpyrrolidin-1-yl]ethyl}-benzofuran-5-yl)benzonitrile
- JNJ-10181457
- 4-(3-(4-piperidin-1-ylbut-1-ynyl)benzyl)morpholine)
- PF-03654746
- (1R,3R)-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide.
- Received May 20, 2010.
- Accepted August 17, 2010.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Histamine H3 Receptors and Sleep-Wake Regulation
