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Individual differences |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |
Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)
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.
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.
- ↑ 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
- ↑ 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