Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next?

Keywords: brexanolone; allopregnanolone (3 ,5 -THP); postpartum depression; fast-acting antidepressant; GABAA receptor; 5 -reduced steroids; 5 -reductase; 3 -HSD EN brexanolone allopregnanolone (3 ,5 -THP) postpartum depression fast-acting antidepressant GABAA receptor 5 -reduced steroids 5 -reductase 3 -HSD 1 6 6 05/18/20 20200514 NES 200514 Introduction Allopregnanolone, today best known as brexanolone and marketed as Zulresso™ for the treatment of postpartum depression is part of only two recently Food and Drug Administration (FDA)-approved fast-acting antidepressants, with esketamine nasal spray, an NMDA receptor antagonist used in treatment-resistant depression with suicidality being the other ([1]). Altogether, stressful condition, hormonal changes, pharmacological treatment (e.g., finasteride, oral contraceptives) may coordinately change GABA SB A sb receptor expression resulting in alterations in receptor function underlying mood disorders. However, it still remains to be clarified the precise treatment targets, including levels of endogenous allopregnanolone, verify altered biosynthetic enzyme expression/function, and GABA SB A sb receptor assembly modifications pre, during, and post-brexanolone treatment. GABA SB A sb receptor expression and neurosteroid biosynthesis in post-partum depression and in general in mood disorders remains underinvestigated. [Extracted from the article]