Mirtazapine relieves depression through a mechanism distinct from SSRIs and SNRIs. Its primary pharmacological action is:

• A Blockade of presynaptic alpha-2 autoreceptors, increasing release of norepinephrine and serotonin ✓
• B Selective inhibition of norepinephrine reuptake with 5-HT3 antagonism
• C Irreversible inhibition of monoamine oxidase A
• D Partial agonism at 5-HT1A receptors combined with dopamine reuptake inhibition

Explanation

Mirtazapine blocks central presynaptic alpha-2 adrenoceptors (autoreceptors and heteroreceptors), disinhibiting release of both norepinephrine and serotonin. Its strong H1 antagonism explains sedation and weight gain, useful properties in depressed patients with insomnia and poor appetite. MAO-B inhibition defines moclobemide and older agents; selective norepinephrine reuptake inhibition with 5-HT3 antagonism resembles a mix of other drugs, and the last option describes neither mirtazapine nor any single marketed antidepressant accurately.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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