By blocking α2-adrenergic autoreceptors and heteroreceptors, NaSSAs enhance adrenergic and serotonergic neurotransmission in the brain involved in mood regulation,[1] notably 5-HT1A-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] The NaSSAs include the following agents: 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.
[5][6] It has completed preliminary preclinical research and may go on to undergo clinical trials.