Allopregnanolone
Allopregnanolone | |
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1-(3-hydroxy-10,13-dimethyl- |
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Other names
3α,5α-Tetrahydroprogesterone |
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Identifiers | |
CAS number | 516-54-1 ![]() |
PubChem | 262961 |
ChemSpider | 17216124 ![]() |
ChEMBL | CHEMBL38856 ![]() |
Jmol-3D images | Image 1 |
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Properties | |
Molecular formula | C21H34O2 |
Molar mass | 318.49 g/mol |
![]() ![]() ![]() Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
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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 GABAA receptors. While allopregnanolone, like other GABAA receptor active neuro[1] steroids such as allotetrahydrodeoxycorticosterone (3α,21-dihydroxy-5α-pregnan-20-one; THDOC), positively modulates all GABAA receptor isoforms, those isoforms containing δ-subunits exhibit greater magnitude potentiation. Allopregnanolone has pharmacological properties similar to other positive modulators of GABAA receptors, including anxiolytic and anticonvulsant activity.[2]
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.[3]
Allopregnanolone aids neurogenesis and has been found to reverse neuron proliferative deficit and cognitive deficits in mouse model of Alzheimer's disease.[4]
See also [edit]
- Tetrahydrocorticosterone (THB)
- Tetrahydrodeoxycorticosterone (THDOC)
Notes [edit]
- ^ Dušková, Michaela. "The influence of low dose finasteride, a type II 5α-reductase inhibitor, on circulating neuroactive steroids". Retrieved 2009-09-17.
- ^ Kokate TG, Svensson BE, Rogawski MA. Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation. J Pharmacol Exp Ther. 1994 Sep;270(3):1223-9. PMID 7932175
- ^ Reddy DS, Rogawski MA. Neurosteroids — Endogenous Regulators of Seizure Susceptibility and Role in the Treatment of Epilepsy. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012. Available from http://www.ncbi.nlm.nih.gov/books/NBK98218/ PubMed PMID 22787590.
- ^ Wang JM, Singh C, Liu L, Irwin RW, Chen S, Chung EJ, Thompson RF, Brinton RD. (2010). Allopregnanolone reverses neurogenic and cognitive deficits in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 107:6498–6503. doi:10.1073/pnas.1001422107 PMID 20231471
Additional references [edit]
- 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. Unknown parameter
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