Pregnanolone
{{Distinguish|Pregnenolone}}
{{About|the 3α,5β-reduced metabolite of progesterone|other pregnanolone isomers of progesterone|Pregnanolone (disambiguation)}}
{{Chembox
| ImageFile = Eltanolone.svg
| ImageClass = skin-invert-image
| ImageSize = 225px
| IUPACName = 3α-Hydroxy-5β-pregnan-20-one
| SystematicName = 1-[(1S,3aS,3bR,5aR,7R,9aS,9bS,11aS)-7-Hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-1-yl]ethan-1-one
| OtherNames = Eltanolone; 5β-Pregnan-3α-ol-20-one; 3α,5β-Tetrahydroprogesterone; 3α,5β-THP; 3α-Hydroxy-5β-tetrahydroprogesterone
|Section1={{Chembox Identifiers
| CASNo = 128-20-1
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BXO86P3XXW
| PubChem = 31402
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 1712
| ChEMBL = 210952
| ChemSpiderID = 29132
| SMILES = CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC[C@H]4[C@@]3(CC[C@H](C4)O)C)C
| InChI = 1/C21H34O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h14-19,23H,4-12H2,1-3H3/t14-,15-,16+,17-,18+,19+,20+,21-/m1/s1
| InChIKey = AURFZBICLPNKBZ-YZRLXODZBF
| StdInChI = 1S/C21H34O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h14-19,23H,4-12H2,1-3H3/t14-,15-,16+,17-,18+,19+,20+,21-/m1/s1
| StdInChIKey = AURFZBICLPNKBZ-YZRLXODZSA-N
}}
|Section2={{Chembox Properties
| C=21 | H=34 | O=2
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|Section3={{Chembox Hazards
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| Section6 = {{Chembox Pharmacology
| AdminRoutes = Intravenous injection
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| HalfLife = 0.9–3.5 hours{{cite journal | vauthors = Gray HS, Holt BL, Whitaker DK, Eadsforth P | title = Preliminary study of a pregnanolone emulsion (Kabi 2213) for i.v. induction of general anaesthesia | journal = Br J Anaesth | volume = 68 | issue = 3 | pages = 272–6 | date = March 1992 | pmid = 1547051 | doi = 10.1093/bja/68.3.272 | s2cid = 19193898 | doi-access = free }}{{cite journal | vauthors = Carl P, Høgskilde S, Nielsen JW, Sørensen MB, Lindholm M, Karlen B, Bäckstrøm T | title = Pregnanolone emulsion. A preliminary pharmacokinetic and pharmacodynamic study of a new intravenous anaesthetic agent | journal = Anaesthesia | volume = 45 | issue = 3 | pages = 189–97 | date = March 1990 | pmid = 2334030 | doi = 10.1111/j.1365-2044.1990.tb14683.x | s2cid = 28358731 | doi-access = free }}
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Pregnanolone, also known as eltanolone, is an endogenous inhibitory neurosteroid which is produced in the body from progesterone.{{cite journal | author = Reddy DS | title = Pharmacology of endogenous neuroactive steroids | journal = Crit Rev Neurobiol | volume = 15 | issue = 3–4 | pages = 197–234 | year = 2003 | pmid = 15248811 | doi = 10.1615/critrevneurobiol.v15.i34.20}} It is closely related to allopregnanolone, which has similar properties.
Biological activity
Pregnanolone is a positive allosteric modulator of the GABAA receptor, as well as a negative allosteric modulator of the glycine receptor.{{cite book|author1=Jürgen Schüttler|author2=Helmut Schwilden|title=Modern Anesthetics|url=https://books.google.com/books?id=JpkkWhPbh2QC&pg=PA278|date=8 January 2008|publisher=Springer Science & Business Media|isbn=978-3-540-74806-9|pages=278–}}
Biological function
Pregnanolone has sedative, anxiolytic, anesthetic, and anticonvulsant effects.{{cite journal |vauthors=Carl P, Høgskilde S, Lang-Jensen T, etal | title = Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans | journal = Acta Anaesthesiol Scand | volume = 38 | issue = 7 | pages = 734–41 |date=October 1994 | pmid = 7839787 | doi = 10.1111/j.1399-6576.1994.tb03987.x | s2cid = 22005284 }} During pregnancy, pregnanolone and allopregnanolone are involved in sedation and anesthesia of the fetus.{{cite journal | vauthors = Mellor DJ, Diesch TJ, Gunn AJ, Bennet L | title = The importance of 'awareness' for understanding fetal pain | journal = Brain Res. Brain Res. Rev. | volume = 49 | issue = 3 | pages = 455–71 | year = 2005 | pmid = 16269314 | doi = 10.1016/j.brainresrev.2005.01.006 | s2cid = 9833426 }}{{cite journal | vauthors = Lagercrantz H, Changeux JP | title = The emergence of human consciousness: from fetal to neonatal life | journal = Pediatr. Res. | volume = 65 | issue = 3 | pages = 255–60 | year = 2009 | pmid = 19092726 | doi = 10.1203/PDR.0b013e3181973b0d | s2cid = 39391626 | url = https://philpapers.org/rec/LAGTEO-5| quote = [...] 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).| doi-access = free }}
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 ({{abbrlink|INN|International Nonproprietary Name}}), but produced unwanted side effects such as convulsions on occasion, and for this reason, was never marketed.{{cite book|author1=Norman Calvey|author2=Norton Williams|title=Principles and Practice of Pharmacology for Anaesthetists|url=https://books.google.com/books?id=lnRlU12Q4h8C&pg=PA110|date=21 January 2009|publisher=John Wiley & Sons|isbn=978-1-4051-9484-6|pages=110–}}
References
{{Reflist}}
{{Progesterone}}
{{Endogenous steroids}}
{{Navboxes
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{{GABA receptor modulators}}
{{GABAA receptor positive modulators}}
{{Glycine receptor modulators}}
{{Xenobiotic-sensing receptor modulators}}
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Category:GABAA receptor positive allosteric modulators
Category:GABAA-rho receptor negative allosteric modulators