What is Norepinephrine?

What It Does and the Role of SNRIs

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Norepinephrine, also known as noradrenaline, is both a hormone and a brain neurotransmitter. It's mainly stored in the neurons of the sympathetic nervous system with small amounts also stored in adrenal tissue.

What Does Norepinephrine Do?

As a hormone, norepinephrine is secreted into the bloodstream by the adrenal glands and works alongside adrenaline, also known as epinephrine, to give the body sudden energy in times of stress, known as the "fight or flight" response.

As a neurotransmitter, norepinephrine passes nerve impulses from one neuron to the next.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Medications that inhibit the reuptake of norepinephrine and serotonin, another neurotransmitter, called serotonin-norepinephrine reuptake inhibitors (SNRIs), have been found to be effective in treating mood disorders like depression, bipolar disorder and anxiety disorders. 

SNRIs are also sometimes prescribed for chronic pain and fibromyalgia.

How SNRIs Work

Serotonin and norepinephrine reuptake inhibitors prevent serotonin and norepinephrine from being absorbed by the brain and change the way these and other neurotransmitters communicate with each other, which in turn helps to boost your mood.

SNRIs for Mood Disorders

The SNRIs approved for use in major depression include Cymbalta (duloxetine), Effexor (venlafaxine) and Pristiq (desvenlafaxine), but there are others approved for other illnesses as well.


Although no antidepressants, including SNRIs, have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of bipolar disorder, they are often prescribed as part of an individual treatment plan.

Common Side Effects of SNRIs

These side effects often go away after a couple weeks, but if they don't or they are particularly bothersome, be sure to contact your doctor.

Common side effects of SNRIs include:

  • Dizziness
  • Dry mouth
  • Sweating more than usual
  • Upset stomach
  • Fatigue
  • Headache
  • Losing your appetite
  • Constipation
  • Sexual difficulties
  • Anxiety
  • Difficulty urinating

The Family of Serotonin-Norepinephrine Reuptake Inhibitors

Each of these SNRIs is a little bit chemically different from the others, which is why they are approved for various illnesses.

  • Effexor (Venlafaxine)

Effexor was the first SNRI to be approved in the United States in 1993. It has been approved by the FDA for depression, panic disorder, social phobia and generalized anxiety disorder (GAD). Effexor inhibits the reabsorption of serotonin quite a bit more than it does norepinephrine.

  • Cymbalta (Duloxetine)

In 2004, Cymbalta was the second SNRI to be approved in the United States.Because of the way it works, it has the highest number of FDA-approvals to treat illnesses, including diabetic peripheral neuropathy, depression, generalized anxiety disorder, fibromyalgia, osteoarthritis and nerve pain. Like Effexor, Cymbalta also favors inhibiting the reabsorption of serotonin over norepinephrine, but to a lesser degree.

  • Pristiq (Desvenlafaxine)

Pristiq, the third SNRI to be approved in 2008, has only been approved to treat major depression so far. Chemically, Pristiq works very similarly to Cymbalta. 

  • Savella (Milnacipran)

The fourth SNRI to be approved in the U.S. in 2009, Savella has only been approved to treat fibromyalgia as of now, though it has been used in France since 1997 to treat major depression as well. Savella works at inhibiting the reabsorption of both serotonin and norepinephrine equally and may even favor norepinephrine, according to some sources.

  • Fetzima (Levomilnacipran)

The most recent member introduced to the SNRI family, Fetzima was approved by the FDA in 2013 and has also only been FDA-approved for treating depression. Fetzima inhibits norepinephrine reabsorption twice as much as serotonin reabsorption, making it unique among the SNRIs.

Schatzburg, A.F., and Schildkraut, J.J. (2000). "Recent Studies on Norepinephrine Systems in Mood Disorders." Retrieved October 8, 2006 from http://www.acnp.org/g4/GN401000092/CH090.html.

Rogers, K. "Norepinephrine." Encyclopaedia Britannica (2015).

"Serotonin and norepinephrine reuptake inhibitors (SNRIs)." Mayo Clinic (2013).

Sansone, R.A., Sansone, L.A. "Serotonin Norepinephrine Reuptake Inhibitors: A Pharmacological Comparison." Innovations in Clinical Neuroscience. 2014;11(3-4):37-42.

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