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# Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Antidepressants that block the reuptake of both serotonin and norepinephrine. Also used for anxiety and some chronic pain; they can raise blood pressure.

Updated 2026-11-01

## What they are

Antidepressants that block both the serotonin and the norepinephrine transporters. Besides depression and anxiety disorders, the extra noradrenergic action makes some of them useful in chronic pain, such as diabetic neuropathic pain and fibromyalgia (duloxetine).

## Mechanism of action

SNRIs bind the serotonin transporter (SERT) and the norepinephrine transporter (NET) and block reuptake of both monoamines. Strengthening descending serotonin and norepinephrine pathways from the brainstem is thought to explain their effect on pain. Unlike tricyclics, they have little affinity for muscarinic, histamine H1 or alpha-1 receptors.

Target: Serotonin transporter (SERT) and norepinephrine transporter (NET)

## Key points

- Noradrenergic effects: raised blood pressure (dose-related with venlafaxine), sweating, tachycardia, urinary hesitancy.
- Same class warnings as SSRIs: suicidality in young people, serotonin syndrome (MAO inhibitors contraindicated), bleeding, hyponatraemia, sexual dysfunction.
- Discontinuation syndrome is especially marked with venlafaxine, which has a short half-life.
- Duloxetine: neuropathic pain, fibromyalgia and chronic musculoskeletal pain; avoided with heavy alcohol use or chronic liver disease (hepatotoxicity).

## Drugs in this class

- [**Venlafaxine** An SNRI antidepressant that blocks serotonin and norepinephrine reuptake. It can raise blood pressure and causes a… Serotonin transporter (SERT) and norepinephrine transporter (NET)](https://durgical.com/en/pharmacology/venlafaxine/)
- [**Duloxetine** An SNRI used for depression and anxiety and also for chronic pain: diabetic neuropathy, fibromyalgia and chronic… Serotonin transporter (SERT) and norepinephrine transporter (NET)](https://durgical.com/en/pharmacology/duloxetine/)

## Others in the class

- Desvenlafaxine
- Levomilnacipran
- Milnacipran

## Test yourself

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

## Why can SNRIs raise blood pressure while SSRIs rarely do?

Blocking the norepinephrine transporter raises norepinephrine at sympathetic synapses, which increases vascular tone and heart rate.

## Which SNRI is used for diabetic neuropathic pain and fibromyalgia?

Duloxetine. Strengthening the descending serotonin and norepinephrine pain-inhibiting pathways is thought to explain the effect.

## Which SNRI is known for a marked discontinuation syndrome, and why?

Venlafaxine, because it and its active metabolite have short half-lives, so levels fall quickly when it is stopped abruptly.

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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 - VENLAFAXINE HYDROCHLORIDE capsule, extended release](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e51f786-3691-4ec4-836b-7f2c9a385aa7) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - DULOXETINE capsule, delayed release](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fb37745f-fb40-4f7f-8143-ea1874c38e1b) (DailyMed (U.S. National Library of Medicine), 2026).

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