Last reviewed 2026-04-22 · How we verify

BF2.649

BF2.649 is a histamine H3 receptor antagonist that increases histamine signaling in the brain to promote wakefulness and cognitive function.

BF2.649 is a histamine H3 receptor antagonist that increases histamine signaling in the brain to promote wakefulness and cognitive function. Used for Narcolepsy type 1, Excessive daytime sleepiness.

At a glance

Mechanism of action

By blocking H3 receptors on histaminergic neurons, BF2.649 prevents negative feedback inhibition and enhances histamine release in the central nervous system. This mechanism promotes wakefulness, improves alertness, and may enhance cognitive performance. The drug is being developed primarily for narcolepsy and other sleep-wake disorders.

Approved indications

• Narcolepsy type 1
• Excessive daytime sleepiness

Common side effects

• Insomnia
• Headache
• Anxiety
• Tremor

Key clinical trials

• Proof of Concept Study on Pitolisant Effect on Autism Spectrum Disorders in Children and Adolescents (PHASE2)
• Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (PHASE3)
• Pitolisant (BF2.649) in the Treatment of EDS in Patients With OSA (PHASE3)
• Study to Demonstrate Cognitive Enhancing Effects of BF2.649 (PHASE2)
• Pitolisant (BF2.649) in the Treatment of Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnoea Syndrome, Treated or Not by Nasal Continuous Positive Airway Pressure, But Still Complaining of Excessive Daytime Sleepiness (PHASE3)
• Determination the Abuse Potential of Pitolisant in Healthy, Non-Dependent Recreational Stimulant Users (PHASE1)
• Effects of BF2.649 in the Treatment of Excessive Daytime Sleepiness in Narcolepsy. (PHASE3)
• Long Term Open Label Study in Narcolepsy With BF2.649 (Pitolisant) (PHASE3)

Primary sources

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