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# Other hypnotics (melatonin agonists and orexin antagonists)

Sleep medicines that do not act on GABA: melatonin and ramelteon stimulate melatonin receptors; suvorexant blocks the wake signal orexin.

Updated 2026-11-01

## What they are

Two newer groups of hypnotics. Melatonin receptor agonists (melatonin, ramelteon) act on the body clock and help with falling asleep. Orexin receptor antagonists (suvorexant and related drugs) quiet the brain's wake-promoting system.

## Mechanism of action

Ramelteon and melatonin stimulate MT1 and MT2 melatonin receptors in the brain's clock. Suvorexant blocks orexin 1 and orexin 2 receptors, so the orexin neuropeptides that keep the brain awake cannot act.

Target: MT1/MT2 melatonin receptors; OX1/OX2 orexin receptors

## Key points

- Ramelteon has no appreciable affinity for the GABA receptor complex and is not a controlled substance.
- Fluvoxamine (a strong CYP1A2 inhibitor) is contraindicated with ramelteon.
- Orexin loss causes narcolepsy, so orexin antagonists are generally avoided in narcolepsy.
- In the United States melatonin is sold as a dietary supplement, with less oversight; contents do not always match the label.

## Drugs in this class

- [**Melatonin** The body's darkness hormone, taken as a medicine or supplement for jet lag and some sleep-timing problems. Evidence… Melatonin receptor MT1](https://durgical.com/en/pharmacology/melatonin/)
- [**Ramelteon** A melatonin receptor agonist for trouble falling asleep. It does not act on GABA, is not a controlled substance and… Melatonin receptor MT1](https://durgical.com/en/pharmacology/ramelteon/)
- [**Suvorexant** An orexin receptor antagonist for insomnia. It blocks the brain's wake signal; it can cause next-day drowsiness and… Orexin receptor type 2 (OX2)](https://durgical.com/en/pharmacology/suvorexant/)

## Others in the class

- Tasimelteon
- Lemborexant
- Daridorexant

## Test yourself

Think of the answer, then tap the question to see it.

## Which receptors does ramelteon stimulate?

The MT1 and MT2 melatonin receptors.

## How does suvorexant promote sleep?

It blocks orexin 1 and 2 receptors, switching off a wake-promoting signal.

## Which antidepressant is contraindicated with ramelteon?

Fluvoxamine, a strong CYP1A2 inhibitor.

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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 - RAMELTEON tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c1ba52a-8e7a-844a-6c48-d1c9bf9fff0e) (DailyMed (U.S. National Library of Medicine), 2026); [Suvorexant: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a614046.html) (MedlinePlus (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 22 (McGraw Hill, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N05C) (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/other-hypnotics/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/other-hypnotics/