Current and Emerging Options for the Drug Treatment of Narcolepsy

摘要: Narcolepsy/hypocretin deficiency (now called type 1 narcolepsy) is a lifelong neurologic disorder with well-established diagnostic criteria and etiology. Narcolepsy chronic sleep characterized by excessive daytime sleepiness (EDS) symptoms of dissociated rapid eye movement such as cataplexy (sudden loss muscle tone), hypnagogic hallucinations (sensory events that occur at the transition from wakefulness to sleep), paralysis (inability perform movements upon wakening or onset), nocturnal disruption. As these are often disabling, most patients need life-long treatment. The treatment narcolepsy well defined, and, traditionally, amphetamine-like stimulants (i.e., dopaminergic release enhancers) have been used for clinical management improve EDS attacks, whereas tricyclic antidepressants anticataplectics. However, treatments evolved better-tolerated compounds modafinil armodafinil (for EDS) adrenergic/serotonergic selective reuptake inhibitors (as anticataplectics). In addition, night-time administration short-acting sedative, γ-hydroxybutyrate (sodium oxybate), has cataplexy. These therapies almost always needed in combination non-pharmacologic behavioral modification). A series new drugs currently being tested animal models humans. include wide variety hypocretin agonists, melanin-concentrating hormone receptor antagonists, antigen-specific immunopharmacology, histamine H3 antagonists/inverse agonists (e.g., pitolisant), which proposed specific therapeutic applications, including Alzheimer’s disease, attention-deficit hyperactivity disorder, epilepsy, more recently, narcolepsy. Even though current strictly symptomatic, based on present state knowledge pathophysiology narcolepsy, we expect pathophysiology-based will be available near future.