Brexanolone (allopregnanolone) is approved for postpartum depression. Its mechanism of action primarily involves:

• A Positive allosteric modulation of GABA-A receptors at the neurosteroid binding site ✓
• B Serotonin-norepinephrine reuptake inhibition
• C Progesterone receptor agonism in limbic areas
• D Selective sigma-1 receptor agonism reversing neuroinflammation

Explanation

Brexanolone is the synthetic form of allopregnanolone (3α-hydroxy-5α-pregnan-20-one), a neuroactive steroid metabolite of progesterone. It acts as a positive allosteric modulator of both synaptic and extrasynaptic GABA-A receptors at a distinct neurosteroid binding site (different from benzodiazepine or barbiturate sites). Post-partum depression is linked to a sharp drop in allopregnanolone levels after delivery; brexanolone replaces this, restoring GABAergic tone and resolving symptoms. It is given as a 60-hour IV infusion and is not a SNRI, progesterone agonist, or sigma agonist.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.