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; also abbreviated as THP or THPROG) 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 neuro steroids 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 may serve as an endogenous anticonvulsant and play a role in catamenial epilepsy.

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

See also

• Tetrahydrocorticosterone (THB)
• Tetrahydrodeoxycorticosterone (THDOC)

Additional 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.