Wake-promoting agents and narcolepsy drugs
Non-amphetamine medicines that reduce excessive daytime sleepiness in narcolepsy, sleep apnoea or shift work; sodium oxybate also treats cataplexy.
What they are
A group of drugs for excessive daytime sleepiness. Modafinil and armodafinil block dopamine reuptake; solriamfetol blocks noradrenaline reuptake; pitolisant blocks histamine H3 receptors; sodium oxybate (GHB) is taken at night and acts through GABA-B receptors. None cures the sleep disorder; in sleep apnoea they treat the sleepiness, not the airway.
Mechanism of action
Each drug raises the activity of a wake-promoting signal: dopamine (modafinil, armodafinil), noradrenaline (solriamfetol) or histamine released when the H3 brake is blocked (pitolisant). Sodium oxybate works differently: it is taken at night and is thought to act through GABA-B receptors; it reduces daytime sleepiness and cataplexy.
Target: Dopamine transporter (DAT); noradrenaline transporter (NET); histamine H3 receptor; GABA-B receptor
Drugs in this class
- ModafinilA wake-promoting drug for excessive sleepiness in narcolepsy, sleep apnoea and shift work. It blocks dopamine…Dopamine transporter (DAT)
- ArmodafinilThe R-enantiomer of modafinil, used for the same kinds of excessive sleepiness. It shares modafinil's rash and…Dopamine transporter (DAT)
- SolriamfetolA wake-promoting drug for daytime sleepiness in narcolepsy or obstructive sleep apnoea. It blocks noradrenaline…Noradrenaline transporter (NET)
- PitolisantA histamine H3 receptor blocker for daytime sleepiness and cataplexy in narcolepsy. It can prolong the QT interval and…Histamine H3 receptor
- Sodium oxybateThe sodium salt of GHB, taken at night for cataplexy and daytime sleepiness in narcolepsy. A strong CNS depressant…GABA-B receptor
Others in the class
- Methylphenidate and amphetamines (stimulants; see ADHD agents)
Test yourself
Think of the answer, then tap the question to see it.
Which wake-promoting drug is taken at night, in bed?
Sodium oxybate, which reduces cataplexy and daytime sleepiness.
How does pitolisant increase wakefulness?
It blocks the histamine H3 receptor, a brake on histamine release, so wake-promoting histamine rises.
What must happen if a rash appears on modafinil?
The drug is stopped unless the rash is clearly unrelated, because of the risk of SJS and DRESS.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - MODAFINIL tablet (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - SODIUM OXYBATE solution (DailyMed (U.S. National Library of Medicine), 2026); Pitolisant: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.