DESCRIPTION
Allopregnanolone, is a neurosteroid that it is also used as a medication, to treat postpartum depression.
It acts as a positive allosteric modulator of the GABAA receptor, the major biological target of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).
Brexanolone was approved for medical use in the United States in 2019 with commercial sales expected to begin in June 2019. The long administration time, as well as the cost of US$34,000, have raised concerns about accessibility for many women.
CLASSIFICATION
- AA
- BB
INDICATIONS
PHARMACOKINETICS
MOLECULAR MECHANISM
5-alpha-reductase/SRD5A1
3-alpha-hydroxysteroid dehydrogenase/AKR1C1
17beta-estradiol 17-dehydrogenase/HSD17B1
Roles of brain 17β-HSD10 in the metabolism of allopregnanolone (ALLOP). ALLOP is a positive steroid modulator of GABAA receptors that potentiates GABA to increase the opening of Cl− channels. ALLOP is generated from 5α-dihydroprogesterone (DHP) by cytosolic 3α-HSD3 catalysis (NADPH), whereas ALLOP is oxidized to 5α-DHP that has no effect on GABAA receptors by the catalysis of mitochondrial 17β-HSD10 (HSD17B1) with the concomitant reduction of NAD+. —• indicates the binding sites of individual modulators on the GABAA receptor.
PHARMACOGENOMICS
SIDE EFFECTS
TOXICITY
RESISTANCE
DEPENDENCE AND WITHDRAW
