Noradrenergic and specific serotonergic antidepressant

Noradrenergic and specific serotonergic antidepressants (NaSSAs) are a class of psychiatric drugs used primarily as antidepressants.^[1] They act by antagonizing the α₂-adrenergic receptor and certain serotonin receptors such as 5-HT_2A and 5-HT_2C,^[1] but also 5-HT₃,^[1] 5-HT₆, and/or 5-HT₇ in some cases. By blocking α₂-adrenergic autoreceptors and heteroreceptors, NaSSAs enhance adrenergic and serotonergic neurotransmission in the brain involved in mood regulation,^[1] notably 5-HT_1A-mediated transmission.^[2] In addition, due to their blockade of certain serotonin receptors, serotonergic neurotransmission is not facilitated in unwanted areas, which prevents the incidence of many side effects often associated with selective serotonin reuptake inhibitor (SSRI) antidepressants;^[1][3] hence, in part, the "specific serotonergic" label of NaSSAs.^[2]

Chemical structure of the prototypical NaSSA mirtazapine (original brand name Remeron)

List of NaSSAs

The NaSSAs include the following agents:

• Aptazapine (CGS-7525A)
• Esmirtazapine (ORG-50,081)
• Mianserin (Bolvidon, Norval, Tolvon)^[4]
• Mirtazapine (Norset, Remeron, Avanza, Zispin)^[4]
• Setiptiline/teciptiline (Tecipul)

Notably, all of these compounds are analogues and are also classified as tetracyclic antidepressants (TeCAs) based on their chemical structures.

S32212, a structurally novel NaSSA with an improved selectivity profile (e.g., no antihistamine effects, etc.), was reported in 2012.^[5][6] It has completed preliminary preclinical research and may go on to undergo clinical trials.

See also

• Serotonin antagonist and reuptake inhibitor (SARI)
• Serotonin modulator and stimulator (SMS)
• Norepinephrine-dopamine disinhibitor (NDDI)
• Tetracyclic antidepressant
• Norepinephrine–dopamine reuptake inhibitor
• Atypical antidepressant