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[Possible roles of brain histamine H3 receptors and the pharmacology of its ligands].
Japanese Journal of Psychopharmacology 1995 April
The discovery of the presynaptic histamine H3 receptors confirmed the idea that histamine is a neurotransmitter in the mammalian brain. The H3 receptors (autoreceptors) regulate the release and synthesis of histamine. The H3 receptors also modulate the other neurotransmitters (heteroreceptors). Subclasses of H3 antagonist binding sites were found in the brain (H3A and H3B). The regulation of noradrenaline release is reported to be mediated by H3A rather than H3B. The H3 binding site belongs to the class of receptors coupled to G-proteins. Besides the molecular data, this review focuses on the functional roles of H3 receptors in the brain and discusses the possible use of H3 ligands for neurobehavioral disorders. The pharmacological data of H3 ligands may provide clinical candidates for CNS disorders in which histamine plays important roles in mental and behavioral functions. Especially, H3 antagonists may be useful for CNS disorders such as narcolepsy, dementia, epilepsy, and obesity, while H3 agonists may provide for anxiety, insomnia, migraine. However, these suggestions are still preliminary and further clinical research is needed, although potent and safe novel H3 ligands are being developed.
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