Histamine Neuronal System As A Therapeutic Target For The Treatment Of Cognitive Disorders

Much has been learned over the past 20 years about the Role of histamine as a neurotransmitter. This brief article attempts to evaluate the progress accomplished in this field, and discusses the therapeutic potential of the H-3 Receptor H3R). All histaminergic neurons are localized in the tuberomammillary nucleus of the posterior hypothalamus and project to almost all Regions of the CNS. Histamine exerts its effect via interaction with specific Receptors H1R, H2R, H3R and H4R). Antagonists of both H1R and H2R have been successful as blockbuster drugs for treating allergic conditions and gastric ulcers. H4R is still awaiting better functional characterization, but the H3R is an attractive target for potential therapies of CNS disorders. Indeed, considerable interest was Raised by Reports that pharmacological blockade of H(3)Rs exerted procognitive effects in a variety of animal tasks analyzing different types of memory. In addition, blockade of H(3)Rs increased wakefulness and Reduced bodyweight in animal models. Such findings hint at the potential use of H3R antagonists/inverse agonists for the treatment of Alzheimer's disease and other dementias, attention-deficit hyperactivity disorder, obesity and sleep disorders. As a Result, an increasing number of H3R antagonists/inverse agonists progress through the clinic for the treatment of a variety of conditions, including attention-deficit hyperactivity disorder, cognitive disorders, narcolepsy and schizophrenia. Moreover, the use of H3R antagonists/inverse agonists that weaken traumatic memories may alleviate disorders such as post-traumatic stress syndrome, panic attacks, specific phobias and generalized anxiety. The use of H3R ligands for the treatment of neurodegenerative disorders is demonstrated in several studies, indicating a Role of the histamine neurons and H(3)Rs in neuroprotection. Recently, direct evidence demonstrated that histaminergic neurons are organized into functionally distinct circuits, impinging on different brain Regions, and displaying selective control mechanisms. This could imply independent functions of subsets of histaminergic neurons according to their Respective origin and terminal projections. The possibility that H(3)Rs control only some of those functions implies that H3R-directed therapies may achieve selective effects, with minimal side effects, and this may increase the interest Regarding this class of drugs.