Mirtazapine

Mirtazapine

Mirtazapine has a unique mechanism of action. It inhibits norepinephrine α2 auto- and hetero-receptors (shown present on a norepinephrine and a serotonin neuron). The inhibition of the α2 auto-receptors results in an increase in NE neurotransmission from the norepinephrine neurons (1). Interestingly, the

inhibition of the α2 hetero-receptors also causes an increase in 5-HT neurotransmission from the serotonergic neurons (2). Thus, this one receptor has two effects: a down regulation of post-synaptic norepinephrine receptors (3) and a down-regulation of non-antagonized post-synaptic serotonin receptors (4). Note that mirtazapine is also an antagonist for the 5HT2A&C and 5HT3 receptors, which potentially could lead to enhanced antidepressant activity (5HT2 receptors) and decreased risk of GI side effects (5HT3 receptors).

1

Mirtazepine’s main mechanism of antidepressant action is the same as the SSRI’s and tricyclics. 

2

The increased presence of noradrenaline in the synapse leads to stimulation of dendritic norepinephrine hetero-receptors on the serotonin neuron. 

3

Based on mechanism of action, mirtazepine should cause less nausea than SSRI’s.