The pharmacologic profile of mirtazapine.

Jan 1, 1996The Journal of clinical psychiatry

How Mirtazapine Works as a Medicine

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Abstract

Mirtazapine increases noradrenergic and serotonergic transmission.

Mirtazapine has prominent properties that block alpha 2-adrenergic receptors without affecting monoamine reuptake.
Increased firing of noradrenergic and serotonergic neurons has been observed with mirtazapine treatment.
Mirtazapine shows low affinity for 5-HT1A receptors but exhibits effects similar to activating these receptors in certain tests.
Both 5-HT2 and 5-HT3 receptors are specifically blocked by mirtazapine.
The enhancement of noradrenergic and serotonergic transmission is likely related to mirtazapine's therapeutic effects.
Blocking 5-HT2 and 5-HT3 receptors may help reduce side effects linked to nonselective serotonin activation.

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Mirtazapine (Org 3770) is a new antidepressant with prominent alpha 2-adrenergic auto- and heteroreceptor antagonistic properties and no effect on monoamine reuptake. Mirtazapine increases noradrenergic and serotonergic transmission, as measured by on-line microdialysis and by enhancement of noradrenergic locus ceruleus and serotonergic raphe nucleus cell firing. Mirtazapine has a low affinity for 5-HT1A receptors but shows 5-HT1A-agonistic-like effects in a conditioned taste aversion test and by causing lower lip retraction in rats. Mirtazapine therefore causes enhancement of 5-HT1-mediated transmission. Other studies show that both 5-HT2 and 5-HT3 receptors are specifically blocked. The enhancement of both noradrenergic and serotonergic transmission probably underlies the therapeutic activity of mirtazapine. Blockade of 5-HT2 and 5-HT3 receptors possibly prevents side effects associated with nonselective 5-HT activation and may also contribute to the anxiolytic and sleep-improving properties of mirtazapine.

The pharmacologic profile of mirtazapine.

Abstract

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