Allopregnanolone

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Allopregnanolone
Allopregnanolone.png
Identifiers
CAS number 516-54-1 N
PubChem 262961
ChemSpider 17216124 YesY
ChEMBL CHEMBL38856 N
Jmol-3D images Image 1
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 (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
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]

Allopregnanolone decreases the cue-induced reinstatement of extinguished cocaine seeking in rats.[5]

See also[edit]

Notes[edit]

  1. ^ Dušková, Michaela. "The influence of low dose finasteride, a type II 5α-reductase inhibitor, on circulating neuroactive steroids". Retrieved 2009-09-17. 
  2. ^ 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
  3. ^ 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.
  4. ^ 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
  5. ^ Schmoutz, CD; et al. (8 January 2014). "Effects of inhibitory GABA-active neurosteroids on cocaine seeking and cocaine taking in rats.". Psychopharmacology (Berl). PMID 24398823. 

Additional references[edit]