Which antidepressant has mechanisms of action involving 5-HT2A antagonism and α2 receptor antagonism?

The correct response is Mirtazapine, which possesses unique pharmacological properties that involve antagonism at the 5-HT2A receptor and the α2 adrenergic receptor. Mirtazapine is classified as a tetracyclic antidepressant and works by facilitating norepinephrine and serotonin release. By blocking the α2 receptors, mirtazapine removes the negative feedback that inhibits norepinephrine release, thereby increasing norepinephrine levels in the synaptic cleft.

Additionally, its antagonism of the 5-HT2A receptor contributes to its antidepressant effects while also minimizing common side effects associated with other antidepressants, such as anxiety and sexual dysfunction. This dual-action mechanism makes mirtazapine particularly effective for treating depression, including in patients who may not respond well to other antidepressant treatments.

In contrast, other antidepressants listed do not share this specific combination of receptor antagonism. For instance, Fluoxetine primarily functions as a selective serotonin reuptake inhibitor (SSRI), lacking significant activity at the 5-HT2A or α2 receptors. Doxepin, while having some sedative qualities, is primarily a tricyclic antidepressant that works through different mechanisms, mostly involving serotonin