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Allopregnanolone

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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 modulator of GABAA receptors. While allopregnanolone, like other GABAA receptor active neurosteroids 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.[1]

The 5β-epimer of this compound (pregnanolone; 3α-hydroxy-5β-pregnan-20-one) has similar properties to allopregnanolone.

The endogenous production of allopregnanolone starts with the converting of progesterone into dihydroprogesterone by 5α-reductase. After that, 3α-hydroxysteroid oxidoreductase isoenzymes (also referred to as 3α-hydroxysteroid dehydrogenase) converts this intermediate into allopregnanolone.

The 3β-methyl analog of allopregnanolone, 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.[2]

References Edit

  1. 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. PubMed PMID 7932175
  2. Wang JM, Singh C, Liu L, Irwin RW, Chen S, Chung EJ, Thompson RF, Brinton RD. (2010). Allopregnanolone reverses neuron 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

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