Neurobiology of disease
The most recent articles from:
Neurobiol. Dis.
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Neurobiology of disease · Apr 2008
Randomized Controlled Trial Multicenter Study Clinical TrialAn inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients.
Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy, direct onsets of rapid eye movement (REM) sleep from wakefulness (DREMs) and deficiency of orexins, neuropeptides that promote wakefulness largely via activation of histamine (HA) pathways. The hypothesis that the orexin defect can be circumvented by enhancing HA release was explored in narcoleptic mice and patients using tiprolisant, an inverse H(3)-receptor agonist. ⋯ Excessive daytime sleep, unaffected under placebo, was nearly suppressed on the last days of tiprolisant dosing. H(3)-receptor inverse agonists could constitute a novel effective treatment of EDS, particularly when associated with modafinil.