Pregnanolone

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Pregnanolone, also known as eltanolone, is an endogenous inhibitory neurosteroid which is produced in the body from progesterone.[1] It is closely related to allopregnanolone, which has similar properties.[1]

Biological activity

Pregnanolone is a positive allosteric modulator of the GABAA receptor,[1] as well as a negative allosteric modulator of the glycine receptor.[2]

Biological function

Pregnanolone has sedative, anxiolytic, anesthetic, and anticonvulsant effects.[1][2][3] During pregnancy, pregnanolone and allopregnanolone are involved in sedation and anesthesia of the fetus.[4][5]

Biochemistry

Pregnanolone is synthesized from progesterone via the enzymes 5β-reductase and 3α-hydroxysteroid dehydrogenase, with 5β-dihydroprogesterone occurring as a metabolic intermediate. The elimination half-life of pregnanolone is between 0.9 and 3.5 hours.[3][6][7]

Chemistry

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Pregnanolone, also known as 3α,5β-tetrahydroprogesterone (3α,5β-THP) or as 5β-pregnan-3α-ol-20-one, is a naturally occurring pregnane steroid and a derivative of progesterone. Related compounds include allopregnanolone (3α,5α-THP; brexanolone), epipregnanolone (3β,5β-THP), hydroxydione, isopregnanolone (3β,5α-THP), and renanolone.

History

Pregnanolone was first isolated from the urine of pregnant women in 1937.[3] Its anesthetic properties were first demonstrated in animals in 1957.[3]

Research

Pregnanolone was investigated for clinical use as a general anesthetic under the name eltanolone (INNTooltip International Nonproprietary Name), but produced unwanted side effects such as convulsions on occasion, and for this reason, was never marketed.[2][8][3]

References

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