It is also possible that neurosteroids like allopregnanolone may act on other targets, including membrane progesterone receptors, T-type voltage-gated calcium channels, and others, to mediate antidepressant effects. Pharmacology
Pharmacokinetics
Brexanolone has low oral bioavailability of less than 5%, necessitating non-oral administration. The volume of distribution of brexanolone is approximately 3 L/kg. Its plasma protein binding is more than 99%. Brexanolone is metabolized by keto-reduction mediated via aldo-keto reductases. The compound is also conjugated by glucuronidation via glucuronosyltransferases and sulfation via sulfotransferases. It is not metabolized importantly by the cytochrome P450 system. The three main metabolites of brexanolone are inactive. The elimination half-life of brexanolone is 9 hours. Its total plasma clearance is 1 L/h/kg. It is excreted 47% in feces and 42% in urine. Less than 1% is excreted as unchanged brexanolone. Chemistry
Allopregnanolone is a pregnane (C21) steroid and is also known as 5α-pregnan-3α-ol-20-one, 5α-Pregnane-3α-ol-20-one, 3α-hydroxy-5α-pregnan-20-one, or 3α,5α-tetrahydroprogesterone (3α,5α-THP). It is closely related structurally to 5-pregnenolone (pregn-5-en-3β-ol-20-dione), progesterone (pregn-4-ene-3,20-dione), the isomers of pregnanedione (5-dihydroprogesterone; 5-pregnane-3,20-dione), the isomers of 4-pregnenolone (3-dihydroprogesterone; pregn-4-en-3-ol-20-one), and the isomers of pregnanediol (5-pregnane-3,20-diol). In addition, allopregnanolone is one of four isomers of pregnanolone (3,5-tetrahydroprogesterone), with the other three isomers being pregnanolone (5β-pregnan-3α-ol-20-one), isopregnanolone (5α-pregnan-3β-ol-20-one), and epipregnanolone (5β-pregnan-3β-ol-20-one). Biosynthesis
The biosynthesis of allopregnanolone in the brain starts with the conversion of progesterone into 5α-dihydroprogesterone by 5α-reductase. After that, 3α-hydroxysteroid dehydrogenase converts this intermediate into allopregnanolone. Allopregnanolone in the brain is produced by cortical and hippocampus pyramidal neurons and pyramidal-like neurons of the basolateral amygdala.
Treatment
MEWDS is a self limited disease with excellent visual recovery within 2-10 weeks. However residual symptoms including photopsia may persist for months. == References ==