Abstract: Pitolisant, a selective histamine H3 receptor inverse agonist, promotes wakefulness by blocking H3 autoreceptor-mediated feedback inhibition to elevate central histamine levels. It is clinically indicated for wake promotion in narcolepsy. The development journey of pitolisant spans over two decades, encompassing extensive preclinical and clinical research. These studies have demonstrated both sustained efficacy in managing narcolepsy and a favorable long-term safety profile. Notably, pitolisant received formal marketing authorization from China's National Medical Products Administration (NMPA) for treating excessive daytime sleepiness or cataplexy in adult narcolepsy patients. This approval addresses an unmet medical need in China's therapeutic landscape, providing patients with a safe, effective, and well-tolerated novel therapeutic option. This article will summarize the basic and clinical research progress of pitolisant from the aspects of development history, preclinical studies and pharmacological effects, clinical research and indications, medication guidelines, and safety, aiming to provide a scientific basis for the clinical treatment of narcolepsy.

Key words: pitolisant, narcolepsy, H3 receptor inverse agonist