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# 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.

Updated Nov 1, 2026

## 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

## Key points

- Modafinil and armodafinil can cause Stevens-Johnson syndrome and DRESS: they are stopped at the first rash.
- Modafinil, armodafinil and pitolisant make hormonal contraceptives less reliable; another method is used during treatment and for weeks after stopping.
- Sodium oxybate is GHB: it is contraindicated with alcohol and sedative hypnotics and is dispensed only through a restricted programme.
- In obstructive sleep apnoea these drugs treat the sleepiness only; the airway treatment continues.

## Drugs in this class

- [**Modafinil** A wake-promoting drug for excessive sleepiness in narcolepsy, sleep apnoea and shift work. It blocks dopamine… Dopamine transporter (DAT)](https://durgical.com/en/pharmacology/modafinil/)
- [**Armodafinil** The R-enantiomer of modafinil, used for the same kinds of excessive sleepiness. It shares modafinil's rash and… Dopamine transporter (DAT)](https://durgical.com/en/pharmacology/armodafinil/)
- [**Solriamfetol** A wake-promoting drug for daytime sleepiness in narcolepsy or obstructive sleep apnoea. It blocks noradrenaline… Noradrenaline transporter (NET)](https://durgical.com/en/pharmacology/solriamfetol/)
- [**Pitolisant** A histamine H3 receptor blocker for daytime sleepiness and cataplexy in narcolepsy. It can prolong the QT interval and… Histamine H3 receptor](https://durgical.com/en/pharmacology/pitolisant/)
- [**Sodium oxybate** The sodium salt of GHB, taken at night for cataplexy and daytime sleepiness in narcolepsy. A strong CNS depressant… GABA-B receptor](https://durgical.com/en/pharmacology/sodium-oxybate/)

## 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.

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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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=944daf47-49a6-93ca-e348-4a0f1b6d937e) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - SODIUM OXYBATE solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5a9e9045-f04d-46eb-8396-2495c6090a31) (DailyMed (U.S. National Library of Medicine), 2026); [Pitolisant: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a619055.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N06BA) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/classes/wake-promoting-agents-and-narcolepsy-drugs/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/wake-promoting-agents-and-narcolepsy-drugs/