title: Role of the Histamine H3Receptor in the Central Nervous System.
abstract: The Gi/oprotein-coupled histamine H3receptor is distributed throughout the central nervous system including areas like cerebral cortex, hippocampus and striatum with the density being highest in the posterior hypothalamus, i.e. the area in which the histaminergic cell bodies are located. In contrast to the other histamine receptor subtypes (H1, H2and H4), the H3receptor is located presynaptically and shows a constitutive activity. In detail, H3receptors are involved in the inhibition of histamine release (presynaptic autoreceptor), impulse flow along the histaminergic neurones (somadendritic autoreceptor) and histamine synthesis. Moreover, they occur as inhibitory presynaptic heteroreceptors on serotoninergic, noradrenergic, dopaminergic, glutamatergic, GABAergic and perhaps cholinergic neurones. This review shows for four functions of the brain that the H3receptor represents a brake against the wake-promoting, anticonvulsant and anorectic effect of histamine (via postsynaptic H1receptors) and its procognitive activity (via postsynaptic H1and H2receptors). Indeed, H1agonists and H3inverse agonists elicit essentially the same effects, at least in rodents; these effects are opposite in direction to those elicited by brain-penetrating H1receptor antagonists in humans. Although the benefit for H3inverse agonists for the symptomatic treatment of dementias is inconclusive, several members of this group have shown a marked potential for the treatment of disorders associated with excessive daytime sleepiness. In March 2016, the European Commission granted a marketing authorisation for pitolisant (WakixR) (as the first representative of the H3inverse agonists) for the treatment of narcolepsy.
authors: Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany. e.schlicker@uni-bonn.de.
authors: Eberhard
authors: E
authors: Schlicker
authors: Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.
authors: Markus
authors: M
authors: Kathmann
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism; D017442:Histamine Agonists / Q000494:pharmacology / Q000627:therapeutic use; D006633:Histamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018100:Receptors, Histamine H3 / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D017442:Histamine Agonists; D006633:Histamine Antagonists; D018100:Receptors, Histamine H3; D006632:Histamine
keywords: Epileptic seizures; Food intake; Histamine H3 receptor; Histaminergic neurones; Learning and memory; Narcolepsy; Noradrenergic neurones; Pitolisant; Presynaptic receptors; Sleep-wake regulation