Mirtazapine is an antidepressant introduced by Organon International in 1996 used for the treatment of moderate to severe depression. Mirtazapine has a tetracyclic chemical structure and is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). It is the only tetracyclic antidepressant that has been approved by the Food and Drug Administration to treat depression. (In Vitro):Mirtazapine can antagonize the adrenergic α2-autoreceptors and α2-heteroreceptors as well as block 5-HT2 and 5-HT3 receptors. Mirtazapine enhances the release of norepinephrine and 5-HT1A-mediated serotonergic transmission.The cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4 are mainly responsible for Mirtazapine's metabolism.Mirtazapine (10 μM) significantly reduces activation-induced release of cytokine/chemokine mediators from human CD14+ monocytes in vitro.(In Vivo):Mirtazapine (1-20 mg/kg; intraperitoneal injection; once; C57BL/6 mice) treatment strikingly and dose-dependently inhibits Con A-induced liver injury.Mirtazapine treatment inhibits hepatic macrophage/monocyte activation, decreases hepatic macrophage/monocyte-derived pro-inflammatory cytokine (e.g., TNFα) and chemokine (e.g., CXCL1 and CXCL2) production, suppression of Con A-induced increases in the hepatic expression of the neutrophil relevant endothelial cell adhesion molecule ICAM-1, with the resultant significant reduction in neutrophil recruitment into the liver.