Introduction: Narcolepsy is a rare sleep disorder characterized by excessive 
daytime sleepiness, cataplexy, disturbed nocturnal sleep, hypnagogic 
hallucinations, and sleep paralysis. Pitolisant is a first-in-class drug acting 
on histamine 3 receptors and indicated for the treatment of narcolepsy. This 
article aims to review pitolisant.Areas covered: In this paper the chemical 
properties, mechanism of action, pharmacokinetics, clinical efficacy and safety 
of pitolisant was introduced, and the development course of drugs for treating 
narcolepsy is also briefly described. We performed a systematic review of the 
literature using PubMed and the following keywords were used: 'pitolisant' and 
'narcolepsy', 'cataplexy' and 'excessive daytime sleepiness' and 'histamine 3 
receptor'.Expert opinion: Pitolisant is a histamine 3 receptor 
antagonist/inverse agonist. It can activate histamine release in the brain and 
enhances wakefulness. Clinical studies showed that pitolisant significantly 
decreased excessive daytime sleepiness and cataplexy rate versus placebo. 
Pitolisant was well tolerated, common adverse reactions were headache, insomnia, 
nausea, and anxiety.