Symptoms of narcolepsy include excessive daytime sleepiness (EDS), which, although not specific to narcolepsy, is a characteristic of the disorder present in all patients, as it is a requirement for diagnosis. The onset of narcolepsy most commonly occurs in the second decade of life, though diagnosis is often delayed by several years. Narcolepsy, a chronic, disabling neurologic disorder of hypersomnolence, affects an estimated 20–67 people per 100,000 worldwide. This review summarises the mechanisms of action, pharmacokinetics, efficacy, and safety/tolerability of recently approved and emerging treatments for narcolepsy. Several new agents are being developed and tested as potential treatments for EDS and cataplexy associated with narcolepsy these agents include novel oxybate formulations (once-nightly low sodium ), a selective norepinephrine reuptake inhibitor (AXS-12), and a product combining modafinil and an astroglial connexin inhibitor (THN102). Pitolisant, an H3R antagonist, and solriamfetol, a dopamine and norepinephrine reuptake inhibitor, are the most recently approved treatments for EDS associated with narcolepsy in the European Union (pitolisant) and the USA (pitolisant and solriamfetol). Modulation of γ-aminobutyric acid B (GABA B) receptors or histamine H 3 receptors (H3Rs) has effects on both EDS and cataplexy. In general, medications that increase the release, or inhibit the reuptake, of norepinephrine or dopamine have wake-promoting effects and are useful in managing EDS, whereas medications that inhibit serotonin or norepinephrine reuptake have anticataplectic effects. sodium oxybate, venlafaxine), and treating the symptoms of disturbed nocturnal sleep, sleep paralysis and sleep-related hallucinations (e.g. modafinil, armodafinil, stimulants), reducing cataplexy attacks (e.g. Treatments for narcolepsy are aimed at improving wakefulness (e.g. Narcolepsy is a chronic, disabling neurologic disorder characterised by excessive daytime sleepiness (EDS) and, in up to 60% of patients, cataplexy.
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