[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/) › Nortriptyline

# Nortriptyline

## TCAs?

Tricyclic antidepressants (TCAs)

A secondary-amine tricyclic antidepressant: less sedating than amitriptyline, used for depression and nerve pain. Dangerous in overdose.

Updated Nov 12, 2026

## Quick facts

**Group**
[Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/)

**Target**
Noradrenaline transporter (NET), and to a lesser degree the serotonin transporter (SERT)

**Used for**
Depression · Off-label · Off-label

**Key effects**
Dry mouth · Drowsiness · Fast heart rate and dizziness

**Monitor**
Mood and suicidal thoughts · ECG and blood pressure

**ATC**
N06AA10

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

On this page

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

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

- Study Test yourself

- Connections Connections

## Mechanism of action

⇄**Noradrenaline transporter (NET), and to a lesser degree the serotonin transporter (SERT)**Nortriptyline

ⓘ The figure shows nortriptyline bound to the dopamine transporter of the fruit fly, a close relative of the human noradrenaline transporter; it blocks the same central site.

**Target in 3D:** Noradrenaline transporter (NET), and to a lesser degree the serotonin transporter (SERT). PDB structure 4M48 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/4M48) · Drag to rotate · pinch to zoom

Nortriptyline is the demethylated (secondary amine) metabolite of amitriptyline. It blocks reuptake of noradrenaline more than serotonin, so more transmitter stays in the synapse; over weeks, receptor adaptations relieve depression and dampen pain signals in the spinal cord. Like other tricyclics it also blocks muscarinic, histamine H1 and alpha-1 receptors (less than tertiary amines), and cardiac sodium channels, which explains its toxicity in overdose.

- Blocks noradrenaline (and some serotonin) reuptake
- More transmitter in the synapse; adaptation over weeks
- Mood improves; descending pain inhibition is strengthened
- Also blocks muscarinic, H1, alpha-1 receptors and Na+ channels

## Indications

- Depression [Major depressive disorder →](https://durgical.com/en/conditions/major-depressive-disorder/)
- Off-label: nerve pain after shingles (post-herpetic neuralgia) [Herpes zoster (shingles) →](https://durgical.com/en/conditions/herpes-zoster/)
- Off-label: panic disorder [Panic disorder →](https://durgical.com/en/conditions/panic-disorder/)
- Off-label: aid to stop smoking [Tobacco use disorder →](https://durgical.com/en/conditions/tobacco-use-disorder/)

## Adverse effects

### Common

- Dry mouth, constipation and difficulty passing urine
- Drowsiness, weakness or tiredness
- Fast heart rate and dizziness
- Appetite or weight change; sweating
- Changes in sex drive or ability

### Serious (rare, important)

- Suicidal thoughts in young people (boxed warning)
- Arrhythmias, conduction delay, heart attack and stroke; unmasking of Brugada syndrome
- Angle-closure glaucoma
- Overdose: seizures, coma and fatal arrhythmias

## Contraindications

- MAO inhibitors now or within the previous two weeks; starting it during linezolid or intravenous methylene blue
- Acute recovery period after a myocardial infarction
- Hypersensitivity to tricyclic antidepressants

## Key interactions

**MAO inhibitors, linezolid, methylene blue and other serotonergic drugs**
Risk of serotonin syndrome.

**CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine, cimetidine)**
Higher nortriptyline levels and toxicity; levels are checked when such a drug is added or stopped.

**Alcohol**
More sedation and a higher risk in overdose.

**Guanethidine**
Its blood-pressure-lowering effect may be blocked.

## What is monitored

- Mood and suicidal thoughts, especially early and after dose changes
- Plasma nortriptyline level at higher doses (it has a therapeutic window)
- ECG and blood pressure in heart disease and older people
- Eye examination for angle-closure risk before starting

## Administration and safety

- Oral capsule or liquid, at the same times each day; started low and increased gradually.
- Not stopped suddenly: headache, nausea and weakness can follow; the dose is tapered.
- Dispensed in limited quantities when suicide risk is a concern, because of overdose toxicity.
- Surgeons and dentists are told that the patient takes it.

## Pregnancy and breastfeeding

Safe use in pregnancy is not established; it is used only when the benefit outweighs the possible risk.

## Nursing care

- Before: ask about heart disease, glaucoma, urinary retention and MAOI use.
- During: ask about mood and suicidal thoughts at each contact; involve family.
- Check pulse and lying/standing blood pressure; teach to rise slowly.
- Teach fluids and fibre for constipation, sun protection and to avoid alcohol.

## Pharmacokinetics

**Absorption**
Oral capsule or liquid.

**Metabolism**
Liver, mainly by CYP2D6; poor metabolisers reach higher levels.

**Onset and duration**
Antidepressant benefit takes weeks.

## Memory aid

NORtriptyline is mostly NORadrenaline: the 'quieter' tricyclic, but still deadly in overdose (the 3 Cs: Convulsions, Coma, Cardiotoxicity).

## Test yourself

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

## Nortriptyline is the active metabolite of which tricyclic?

Amitriptyline (by demethylation).

## Why is nortriptyline less sedating and anticholinergic than amitriptyline?

As a secondary amine it binds muscarinic and H1 receptors less strongly.

## Which drug group can push nortriptyline levels into the toxic range?

CYP2D6 inhibitors such as quinidine, fluoxetine and paroxetine.

## What makes tricyclic overdose lethal?

Sodium-channel block in the heart (wide QRS, arrhythmias), plus seizures and coma.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/nortriptyline/)

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

## Connections

## Related drugs 3

- [Amitriptyline](https://durgical.com/en/pharmacology/amitriptyline/)
- [Imipramine](https://durgical.com/en/pharmacology/imipramine/)
- [Clomipramine](https://durgical.com/en/pharmacology/clomipramine/)

## Related conditions 4

- [Major depressive disorder](https://durgical.com/en/conditions/major-depressive-disorder/)
- [Herpes zoster (shingles)](https://durgical.com/en/conditions/herpes-zoster/)
- [Panic disorder](https://durgical.com/en/conditions/panic-disorder/)
- [Tobacco use disorder](https://durgical.com/en/conditions/tobacco-use-disorder/)

[← Back to the class: Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-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: [Nortriptyline: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682620.html) (MedlinePlus (U.S. National Library of Medicine), 2017); [NORTRIPTYLINE HYDROCHLORIDE capsule](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a904ddf-574a-8a24-e063-6394a90aba3b) (DailyMed (U.S. National Library of Medicine), 2026); [X-ray structure of dopamine transporter elucidates antidepressant mechanism](https://www.rcsb.org/structure/4M48) (RCSB Protein Data Bank, 2013); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N06AA10) (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/nortriptyline/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/nortriptyline/