[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Atypical antidepressants](https://durgical.com/en/pharmacology/classes/atypical-antidepressants/) › Esketamine

# Esketamine

## Atypical antidepressants?

Atypical antidepressants

## Pregnancy: avoid?

Avoided in pregnancy: animal data suggest it may harm the fetus; it is not used while breastfeeding.

The S-form of ketamine as a nasal spray for treatment-resistant depression. Given in a clinic, with observation for dissociation and sedation.

Updated Nov 12, 2026

Also called: S-ketamine

## Quick facts

**Group**
[Atypical antidepressants](https://durgical.com/en/pharmacology/classes/atypical-antidepressants/)

**Target**
NMDA glutamate receptor (GluN1/GluN2)

**Used for**
Treatment-resistant depression in adults

**Key effects**
Dissociation · Nausea · Sleepiness

**Monitor**
Blood pressure before · Sedation · Signs of misuse

**ATC**
N06AX27

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

◎**NMDA glutamate receptor (GluN1/GluN2)**Esketamine

ⓘ The figure shows esketamine (S-ketamine) in the channel pore of the human GluN1–GluN2A NMDA receptor, with glycine and glutamate.

**Target in 3D:** NMDA glutamate receptor (GluN1/GluN2). PDB structure 7EU7 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/7EU7) · Drag to rotate · pinch to zoom

Esketamine is the S-enantiomer of ketamine and blocks the NMDA glutamate receptor channel. The leading explanation of its fast antidepressant effect is that blocking NMDA receptors on inhibitory interneurons causes a burst of glutamate release, AMPA receptor activation and growth-factor signalling (BDNF) that restores synapses in mood circuits. The same channel block produces dissociation, sedation and a rise in blood pressure.

- Blocks the NMDA receptor channel
- Glutamate burst activates AMPA receptors
- BDNF signalling rebuilds synapses in mood circuits
- Side effects: dissociation, sedation, raised blood pressure

## Indications

- Treatment-resistant depression in adults, alone or with an oral antidepressant [Major depressive disorder →](https://durgical.com/en/conditions/major-depressive-disorder/)
- Depressive symptoms in adults with suicidal thoughts or actions, with an oral antidepressant [Suicidal behaviour and suicide risk →](https://durgical.com/en/conditions/suicidal-behaviour-and-suicide-risk/)

## Adverse effects

### Common

- Dissociation (feeling detached from body or surroundings), dizziness, vertigo
- Nausea, vomiting
- Sleepiness, feeling drunk
- Unusual or metallic taste; nasal discomfort
- Raised blood pressure for some hours after a dose

### Serious (rare, important)

- Sedation and breathing problems
- Abuse and misuse (boxed warning)
- Suicidal thoughts (boxed warning)
- Bladder symptoms (frequent, painful urination); thinking or memory problems

## Contraindications

- Aneurysmal blood-vessel disease (brain, chest, abdomen, limbs) or arteriovenous malformation
- History of bleeding in the brain

## Key interactions

**Alcohol, benzodiazepines, opioids and other CNS depressants**
More sedation.

**Nasal corticosteroids or decongestants**
Used at least one hour before the dose.

## What is monitored

- Blood pressure before and after each dose
- Sedation, dissociation and breathing during observation
- Mood and suicidal thoughts
- Signs of misuse

## Administration and safety

- Self-given nasal spray under direct supervision in a certified health-care setting (restricted programme).
- The patient is observed for at least two hours after each dose until stable.
- No food for about two hours and no drink for about half an hour beforehand, to limit nausea.
- No driving or machinery until the next day after a restful sleep; someone else takes the patient home.

## Pregnancy and breastfeeding

Avoided in pregnancy: animal data suggest it may harm the fetus; it is not used while breastfeeding.

## Nursing care

- Before: measure blood pressure; delay the dose if it is too high.
- During: watch for dissociation, sedation and breathing; remeasure blood pressure.
- Before discharge: confirm the patient is stable and has a ride.
- Ask about mood, suicidal thoughts and urinary symptoms at each visit.

## Pharmacokinetics

**Absorption**
Nasal spray; each device gives one spray per nostril.

**Onset and duration**
Antidepressant effect can begin within days, faster than oral antidepressants.

## Memory aid

Esketamine = ketamine's 'S' twin, given 'Supervised': Spray in clinic, Sit and be watched, no Steering wheel until tomorrow.

## Test yourself

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

## Which receptor does esketamine block?

The NMDA glutamate receptor (channel pore).

## Why must patients stay in the clinic after each dose?

Sedation, dissociation and a rise in blood pressure peak in the first hours; they are observed for at least two hours.

## Which vascular conditions rule out esketamine?

Aneurysmal vascular disease, arteriovenous malformation and a history of brain haemorrhage, because of the blood-pressure rise.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/esketamine/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**Pregnancy: avoid**
Avoided in pregnancy: animal data suggest it may harm the fetus; it is not used while breastfeeding.

## Connections

## Related drugs 3

- [Ketamine](https://durgical.com/en/pharmacology/ketamine/)
- [Memantine](https://durgical.com/en/pharmacology/memantine/)
- [Phencyclidine (PCP)](https://durgical.com/en/pharmacology/phencyclidine/)

## Related conditions 2

- [Major depressive disorder](https://durgical.com/en/conditions/major-depressive-disorder/)
- [Suicidal behaviour and suicide risk](https://durgical.com/en/conditions/suicidal-behaviour-and-suicide-risk/)

[← Back to the class: Atypical antidepressants](https://durgical.com/en/pharmacology/classes/atypical-antidepressants/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Esketamine Nasal Spray: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a619017.html) (MedlinePlus (U.S. National Library of Medicine), 2025); [Structure of the human GluN1-GluN2A NMDA receptor in complex with S-ketamine, glycine and glutamate](https://www.rcsb.org/structure/7EU7) (RCSB Protein Data Bank, 2021); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N06AX27) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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