INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad 
of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, 
hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. Treatment 
of narcolepsy remains challenging and current therapy is strictly 
symptomatically based.
AREAS COVERED: The present manuscript is based on an extensive Internet and 
PubMed search from 1990 to 2020. It is focused on the clinical and 
pharmacological properties of pitolisant in the treatment of narcolepsy.
EXPERT OPINION: Currently there is no cure for narcolepsy. Although efforts have 
been made, current treatments do not always allow to obtain an optimal control 
of symptoms. Pitolisant is an antagonist/inverse agonist of the histamine H3 
autoreceptor. Its mechanism of action is novel and distinctive compared to the 
other available therapies for narcolepsy. Clinical trials suggest that 
pitolisant administered at a dose of ≤36 mg/day is an effective treatment option 
for narcolepsy, reducing EDS and cataplexy. Pitolisant is available as oral 
tablets and offers a convenient once-daily regimen. Pitolisant is generally well 
tolerated and showed minimal abuse potential in animals and humans. Long-term 
studies comparing the effectiveness and tolerability of pitolisant with active 
drugs (e.g. modafinil, sodium oxybate) are needed.