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Serotonin Noradrenaline Reuptake Inhibitors ( SNRIs) - Mechanism of Action and Side effects
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• 08/18/25
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Serotonin-noradrenaline reuptake inhibitors (SNRIs) are medications that are evidence-based in the treatment of depression, anxiety, panic disorder and some other mood disorders.
#antidepressants #venlafaxine #duloxetine #snris #milnacipran #pristiq #desvenlafaxine
They block the reuptake of serotonin and norepinephrine, two neurotransmitters released by the presynaptic neurons.
SNRIs are dual-action antidepressants as they increase NA and 5HT in the synapse. SSRIs only increase 5HT.
Although being a dual-action agent increasing 5HT & NA they have a 3rd action on DA in the prefrontal cortex (PFC) but NOWHERE else in the brain.
So they’re not FULL triple-action agents since they do not inhibit the DA transport DAT, but SNRIs can perhaps be considered to have 2.5 actions, rather than just two.
In the PFC, SERTs and NATs are abundant on 5HT & NA nerve terminals but there are very few DATs on dopamine nerve terminals in this part of the brain. NAT performs the role of DAT in the PFC.
Therefore, NAT inhibition also enhances DA levels and increases DA’s diffusion radius.
SNRIs:
Duloxetine
Venlafaxine
Desvenlafaxine
Milnacipran
Side effects:
GI side effects 10%-30%
Weight gain- less than 10%
Sexual dysfunction - less than 30%
Anticholinergic -10%-30%
CNS activation - 10%-30%
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