View source for 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-[(1''S'',3a''S'',3b''R'',5a''R'',7''R'',9a''S'',9b''S'',11a''S'')-7-Hydroxy-9a,11a-dimethylhexadecahydro-1''H''-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
| Appearance = 
| Density = 
| MeltingPt = 
| BoilingPt = 
| Solubility =
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|Section3={{Chembox Hazards
| MainHazards = 
| FlashPt = 
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| Section6 = {{Chembox Pharmacology
| AdminRoutes = [[Intravenous injection]]<ref name="pmid7839787" />
| Bioavail = 
| Excretion = 
| HalfLife = 0.9–3.5 hours<ref name="pmid7839787" /><ref name="pmid1547051">{{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 }}</ref><ref name="pmid2334030">{{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 }}</ref>
| Metabolism = 
| ProteinBound = 
  }}
}}

'''Pregnanolone''', also known as '''eltanolone''', is an [[endogenous]] [[inhibitory postsynaptic potential|inhibitory]] [[neurosteroid]] which is produced in the body from [[progesterone]].<ref name="pmid15248811">{{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}}</ref> It is closely related to [[allopregnanolone]], which has similar properties.<ref name="pmid15248811" />

==Biological activity==
Pregnanolone is a [[positive allosteric modulator]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]],<ref name="pmid15248811" /> as well as a [[negative allosteric modulator]] of the [[glycine receptor]].<ref name="SchüttlerSchwilden2008">{{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–}}</ref>

==Biological function==
Pregnanolone has [[sedative]], [[anxiolytic]], [[anesthetic]], and [[anticonvulsant]] effects.<ref name="pmid15248811" /><ref name="SchüttlerSchwilden2008" /><ref name="pmid7839787">{{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 }}</ref> During [[pregnancy]], pregnanolone and [[allopregnanolone]] are involved in [[sedation]] and [[anesthesia]] of the [[fetus]].<ref name="pmid16269314">{{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 }}</ref><ref name="pmid19092726">{{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 }}</ref>

==Biochemistry==
Pregnanolone is synthesized from [[progesterone]] via the [[enzyme]]s [[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&nbsp;hours.<ref name="pmid7839787" /><ref name="pmid1547051" /><ref name="pmid2334030" />

==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 [[natural product|naturally occurring]] [[pregnane]] [[steroid]] and a [[chemical derivative|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.<ref name="pmid7839787" /> Its anesthetic properties were first demonstrated in animals in 1957.<ref name="pmid7839787" />

==Research==
Pregnanolone was investigated for clinical use as a [[general anesthetic]] under the name ''eltanolone'' ({{abbrlink|INN|International Nonproprietary Name}}), but produced unwanted [[side effect]]s such as [[convulsion]]s on occasion, and for this reason, was never marketed.<ref name="SchüttlerSchwilden2008" /><ref name="CalveyWilliams2009">{{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–}}</ref><ref name="pmid7839787" />

==References==
{{Reflist}}


{{Progesterone}}
{{Endogenous steroids}}
{{Navboxes
| title = [[Biological activity]]
| titlestyle = background:#ccccff
| list1 = 
{{GABA receptor modulators}}
{{GABAA receptor positive modulators}}
{{Glycine receptor modulators}}
{{Xenobiotic-sensing receptor modulators}}
}}

[[Category:5β-Pregnanes]]
[[Category:GABAA receptor positive allosteric modulators]]
[[Category:GABAA-rho receptor negative allosteric modulators]]
[[Category:General anesthetics]]
[[Category:Glycine receptor antagonists]]
[[Category:Neurosteroids]]
[[Category:Pregnane X receptor agonists]]