Pregnanolone Explained

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.

Biological activity

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

Biological function

Pregnanolone has sedative, anxiolytic, anesthetic, and anticonvulsant effects.^[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.

Chemistry

See also: List of neurosteroids.

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. Its anesthetic properties were first demonstrated in animals in 1957.

Research

Pregnanolone was investigated for clinical use as a general anesthetic under the name eltanolone, but produced unwanted side effects such as convulsions on occasion, and for this reason, was never marketed.^[6]

Notes and References

1. Reddy DS . Pharmacology of endogenous neuroactive steroids . Crit Rev Neurobiol . 15 . 3–4 . 197–234 . 2003 . 15248811 . 10.1615/critrevneurobiol.v15.i34.20.
2. Book: Jürgen Schüttler. Helmut Schwilden. Modern Anesthetics. 8 January 2008. Springer Science & Business Media. 978-3-540-74806-9. 278–.
3. Carl P, Høgskilde S, Lang-Jensen T, etal . Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans . Acta Anaesthesiol Scand . 38 . 7 . 734–41 . October 1994 . 7839787 . 10.1111/j.1399-6576.1994.tb03987.x . 22005284 .
4. Mellor DJ, Diesch TJ, Gunn AJ, Bennet L . The importance of 'awareness' for understanding fetal pain . Brain Res. Brain Res. Rev. . 49 . 3 . 455–71 . 2005 . 16269314 . 10.1016/j.brainresrev.2005.01.006 . 9833426 .
5. Lagercrantz H, Changeux JP . The emergence of human consciousness: from fetal to neonatal life . Pediatr. Res. . 65 . 3 . 255–60 . 2009 . 19092726 . 10.1203/PDR.0b013e3181973b0d . 39391626 . [...] the fetus is sedated by the low oxygen tension of the fetal blood and the neurosteroid anesthetics pregnanolone and the sleep-inducing prostaglandin D2 provided by the placenta (36).. free .
6. Book: Norman Calvey. Norton Williams. Principles and Practice of Pharmacology for Anaesthetists. 21 January 2009. John Wiley & Sons. 978-1-4051-9484-6. 110–.