Mirtazapine produces sedation and increased appetite through a receptor mechanism distinct from all other antidepressants. What is this primary mechanism?
- A Blockade of presynaptic alpha-2 adrenergic autoreceptors combined with 5-HT2 and 5-HT3 receptor antagonism ✓
- B Selective inhibition of norepinephrine reuptake at the transporter NET
- C Full agonism at postsynaptic 5-HT1A receptors
- D Irreversible inhibition of monoamine oxidase A
Correct answer: A. Blockade of presynaptic alpha-2 adrenergic autoreceptors combined with 5-HT2 and 5-HT3 receptor antagonism
Explanation
Mirtazapine blocks presynaptic alpha-2 heteroreceptors and autoreceptors, disinhibiting both noradrenergic and serotonergic release, and simultaneously blocks 5-HT2 and 5-HT3 receptors. Blockade of histamine H1 accounts for sedation and weight gain, which are exploited clinically when insomnia and poor appetite accompany depression. It does not inhibit monoamine transporters or MAO, and it is an antagonist, not an agonist, at serotonergic receptors.
Reference: Katzung Basic and Clinical Pharmacology, 16th ed.
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