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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)

Drugs in this class

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 (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - DULOXETINE capsule, delayed release (DailyMed (U.S. National Library of Medicine), 2026).

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