Duloxetine

Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, neuropathic pain and central sensitization. See also [1].

Duloxetine inhibits the reuptake of serotonin and norepinephrine (NE) in the central nervous system. Duloxetine increases dopamine (DA) specifically in the prefrontal cortex, where there are few DA reuptake pumps, via the inhibition of NE reuptake pumps (NET), which is believed to mediate reuptake of DA and NE.^[1][61] Duloxetine has no significant affinity for dopaminergic, cholinergic, histaminergic, opioid, glutamate, and GABA reuptake transporters, however, and can therefore be considered to be a selective reuptake inhibitor at the 5-HT and NE transporters. Duloxetine undergoes extensive metabolism, but the major circulating metabolites do not contribute significantly to the pharmacologic activity.[62][63]

In vitro binding studies using synaptosomal preparations isolated from rat cerebral cortex indicated that duloxetine was approximately 3 fold more potent at inhibiting serotonin uptake than norepinephrine uptake.[64]