How Cymbalta works

Cymbalta (duloxetine HCl) is a balanced and potent (exerting or capable of exerting strong effects, having high affinity for) dual reuptake inhibitor of both serotonin (5-HT) and norepinephrine (NE).

″Balanced″ means that Cymbalta has almost the same affinity for binding to both 5-HT and NE reuptake transporters, based on preclinical data.

The mechanism of action of Cymbalta

The clinical effect of the action of Cymbalta on dopamine is unknown at this time. However, DA and NE are structurally similar; therefore, it is thought that in the prefrontal cortex agents that affect NE additionally have an indirect effect on DA.


  • increases serotonergic and noradrenergic neurotransmission by blocking the reuptake of 5-HT and NE from the synapse. (See Figure 2 for a review of neurotransmission and neurotransmitter reuptake)
  • inhibits dopamine (DA) reuptake to a lesser extent. i


Figure 2:Review of Neurotransmission and Neurotransmitter Reuptake

Although the exact way that Cymbalta works in people is unknown, it is believed to be related to an increase in the activity of serotonin and norepinephrine which are two naturally occurring substances in the brain.

1Eli Lilly and Company. Application Summary for Duloxetine Hydrochloride for Major Depressive Disorder.


Last Update: 12 Oct 15