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Histaminergic transmission in narcolepsy type 1 – therapeutical implications

Mariusz Siemiński

Affiliation and address for correspondence
Aktualn Neurol 2018, 18 (1), p. 21–26
DOI: 10.15557/AN.2018.0003
Abstract

Narcolepsy type 1 (narcolepsy with cataplexy) is a disease manifested by excessive daytime sleepiness, uncontrolled falling asleep, episodes of cataplexy (sudden loss of muscle tone), hypnagogic and hypnopompic hallucinations and sleep paralysis. Due to its clinical course, it significantly reduces the functioning of patients. The aim of the paper is to present actual data on histaminergic transmission in narcolepsy and its clinical implications. The main cause of narcolepsy type 1 is the deficiency of the hypothalamic neurotransmitter orexin/hypocretin. Current therapeutic options, including the use of psychostimulants and anti-cataplectic drugs, are limited and have significant adverse effects. In recent years attention has been given to the role of histaminergic transmission in circadian rhythm control and in the course of narcolepsy. Histaminergic neurons significantly modify action of hypocretin neurons in the control of circadian rhythm. The result of this research was the introduction of the H3R inverse agonist pitolisant in clinical trials. This drug has been shown to be effective in the treatment of daytime sleepiness and cataplexy in patients with type 1 narcolepsy. The success of pitolisant clinical trials demonstrates the therapeutic potential of interventions on histaminergic transmission. Pitolisant – drug influencing the histaminergic transmission efficiently reduces symptoms of narcolepsy type 1. It is a safe molecule, without addiction potential. Due to its discovery the therapeutic armamentarium for narcolepsy type 1 is significantly broadened.

Keywords
narcolepsy, cataplexy, hypocretin, histamine, orexin, pitolisant

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