Allopregnanolone

Allopregnanolone
IUPAC name 1-(3-hydroxy-10,13-dimethyl- 2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro- 1H-cyclopenta[a] phenanthren-17-yl)ethanone
Other names 3α,5α-Tetrahydroprogesterone
Identifiers
CAS number	516-54-1 N
PubChem	262961
ChemSpider	17216124 Y
ChEMBL	CHEMBL38856 N
Jmol-3D images	Image 1
SMILES CC(=O)[C@H]2CC[C@H]1[C@@H]3CCC4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@@]12C
InChI InChI=1S/C21H34O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h14-19,23H,4-12H2,1-3H3/t14?,15-,16+,17-,18+,19+,20+,21-/m1/s1 Y Key: AURFZBICLPNKBZ-JMTGGFPBSA-N Y InChI=1/C21H34O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h14-19,23H,4-12H2,1-3H3/t14?,15-,16+,17-,18+,19+,20+,21-/m1/s1 Key: AURFZBICLPNKBZ-JMTGGFPBBC
Properties
Molecular formula	C21H34O2
Molar mass	318.49 g/mol
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Allopregnanolone (3α-hydroxy-5α-pregnan-20-one or 3α,5α-tetrahydroprogesterone) is a prototypic neurosteroid present in the blood and also the brain. It is a metabolite of progesterone and potent modulator of GABA_A receptors. While allopregnanolone, like other GABA_A receptor active neurosteroids such as allotetrahydrodeoxycorticosterone (3α,21-dihydroxy-5α-pregnan-20-one; THDOC), positively modulates all GABA_A receptor isoforms, those isoforms containing δ-subunits exhibit greater magnitude potentiation. Allopregnanolone has pharmacological properties similar to other positive modulators of GABA_A receptors, including anxiolytic and anticonvulsant activity.

The biosynthesis of allopregnanolone starts with the converting of progesterone into 5α-dihydroprogesterone by 5α-reductase type I. After that, 3α-hydroxysteroid oxidoreductase isoenzymes (also referred to as 3α-hydroxysteroid dehydrogenase) converts this intermediate into allopregnanolone. Anxiety and depression are common side effects of 5α-reductase inhibitors such as finasteride and dutasteride, and they are believed to be caused, in part, by the prevention of the endogenous production of allopregnanolone.

The 5β-epimer of this compound (pregnanolone; 3α-hydroxy-5β-pregnan-20-one) has similar properties to allopregnanolone, and the 3β-methyl analogue, ganaxolone, is under development to treat epilepsy and other conditions.

Allopregnanolone aids neurogenesis and has been found to reverse neuron creation and cognitive deficits in mouse model of Alzheimer’s disease.

References

* Herd, MB,; Belelli D, Lambert JJ. (2007). Neurosteroid modulation of synaptic and extrasynaptic GABA(A) receptors. Pharmacol. Ther. 116(1):20-34. doi:10.1016/j.pharmthera.2007.03.007. 

• Kask K; Bäckström T; Nilsson LG; Sundström-Poromaa I (2008). "Allopregnanolone impairs episodic memory in healthy women". Psychopharmacology 199 (2): 161–8. doi:10.1007/s00213-008-1150-7. PMID 18551282. 
• Chen S; Wang JM; Irwin RW (2011). "Allopregnanolone Promotes Regeneration and Reduces β-Amyloid Burden in a Preclinical Model of Alzheimer's Disease". PLoS ONE 6 (8): e24293. doi:10.1371/journal.pone.0024293. PMC 3168882. PMID 21918687. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3168882.