Mirtazapine

Mirtazapine (Org3770) is a potent and orally active noradrenergic and specific serotonergic antidepressant (NaSSA) agent. Mirtazapine is also a 5-HT₂, 5-HT₃, histamine H1 receptor and α2-adrenoceptor antagonist with pK_i values of 8.05, 8.1, 9.3 and 6.95, respectively^[1][2]. 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^[1].
The cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4 are mainly responsible for Mirtazapine's metabolism^[1].
Mirtazapine (10 μM) significantly reduces activation-induced release of cytokine/chemokine mediators from human CD14⁺ monocytes in vitro^[3]. In Vivo: Mirtazapine (1-20 mg/kg; intraperitoneal injection; once; C57BL/6 mice) treatment strikingly and dose-dependently inhibits Con A-induced liver injury^[3].
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^[3].