SNRIs (Serotonin Norepinephrine Reuptake Inhibitors) are a class of antidepressant drugs capable of treating depression along with a variety of other neurological disorders.

These drugs are fairly new but are gaining popularity due in part to their effectiveness at treating depressive disorders but bolstered by the lack of severe side effects when compared to SSRIs. Additionally, SNRIs have a higher degree of versatility at treating a myriad of conditions.

How They Work: 

SNRIs, like the SSRIs, take advantage of the well established “monoamine hypothesis” which states that so-called “monoamine” neurotransmitters are responsible for moderating depressive conditions. Among these are serotonin, norepinephrine, dopamine and others.

These neurotransmitters moderate a variety of neurological “pathways” which, when appropriately stimulated, can lead to feelings of happiness

SNRIs regulate two of these “monoamines,” serotonin (aka 5-HT) and norepinephrine to increase stimulation of their respective pathways. This is accomplished by preventing their reuptake into the presynaptic cell out of the synaptic cleft.

The more time a neurotransmitter spends in the synaptic cleft, the more postsynaptic stimulation, the more “results.” Stimulation of neurons has consequences, in the case of this pathway, the consequence is reduced levels of depression.

A “good” SNRI will have high affinity for postsynaptic serotonin and norepinephrine transporters and low affinity for the receptors of other neurotransmitters (high specificity). SNRIs should be highly selective to avoid the unpredictable side effects caused by MAOIs and tricyclic antidepressants.

Clinically Available SNRIs:

There are currently a variety of SNRIs on the market, all with slightly varying effects.

All function by a similar mechanism but some have very different effects and treatment capacity.

List of SNRIs:

Duloxetine (Cymbalta, Ariclaim, Xeristar, Yentreve, Duzela):

Also used as a highly effective treatment for fibromyalgia. Used for anxiety disorders and more severe depression

Venlafaxine (Effexor): Most popular and first SNRI. Lower selectivity than other SNRIs which may lead to more side effects.

Milnacipran (Dalcipran,  Ixel, Savella): treats both depression and fibromyalgia.

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Anthony Isaacson

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