Pregnanolone

Pregnanolone
Names
	IUPAC name 3α-Hydroxy-5β-pregnan-20-one
	Systematic IUPAC name 1-[(1S,3aS,3bR,5aR,7R,9aS,9bS,11aS)-7-Hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-1-yl]ethan-1-one
	Other names Eltanolone; 5β-Pregnan-3α-ol-20-one; 3α,5β-Tetrahydroprogesterone; 3α,5β-THP; 3α-Hydroxy-5β-tetrahydroprogesterone
Identifiers
CAS Number	128-20-1 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:1712 ;
ChEMBL	ChEMBL210952;
ChemSpider	29132;
ECHA InfoCard	100.162.192
PubChem CID	31402;
UNII	BXO86P3XXW ;
CompTox Dashboard (EPA)	DTXSID1046342 ;
	InChI InChI=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 Key: AURFZBICLPNKBZ-YZRLXODZSA-N; 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 Key: AURFZBICLPNKBZ-YZRLXODZBF;
	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;
Properties
Chemical formula	C21H34O2
Molar mass	318.501 g·mol−1
Pharmacology
Routes of; administration	Intravenous injection
	Pharmacokinetics:
Biological half-life	0.9–3.5 hours
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Pregnanolone, also known as eltanolone, is an endogenous inhibitory neurosteroid which is produced in the body from progesterone.^[4] It is closely related to allopregnanolone, which has similar properties.^[4]

Biological activity

Pregnanolone is a positive allosteric modulator of the GABA_A receptor,^[4] as well as a negative allosteric modulator of the glycine receptor.^[5]

Biological function

Pregnanolone has sedative, anxiolytic, anesthetic, and anticonvulsant effects.^[4]^[5]^[1] During pregnancy, pregnanolone and allopregnanolone are involved in sedation and anesthesia of the fetus.^[6]^[7]

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.^[1]^[2]^[3]

Chemistry

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.^[1] Its anesthetic properties were first demonstrated in animals in 1957.^[1]

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.^[5]^[8]^[1]

References

^ ^a ^b ^c ^d ^e ^f ^g Carl P, Høgskilde S, Lang-Jensen T, et al. (October 1994). "Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans". Acta Anaesthesiol Scand. 38 (7): 734–41. doi:10.1111/j.1399-6576.1994.tb03987.x. PMID 7839787. S2CID 22005284.
^ ^a ^b Gray HS, Holt BL, Whitaker DK, Eadsforth P (March 1992). "Preliminary study of a pregnanolone emulsion (Kabi 2213) for i.v. induction of general anaesthesia". Br J Anaesth. 68 (3): 272–6. doi:10.1093/bja/68.3.272. PMID 1547051. S2CID 19193898.
^ ^a ^b Carl P, Høgskilde S, Nielsen JW, Sørensen MB, Lindholm M, Karlen B, Bäckstrøm T (March 1990). "Pregnanolone emulsion. A preliminary pharmacokinetic and pharmacodynamic study of a new intravenous anaesthetic agent". Anaesthesia. 45 (3): 189–97. doi:10.1111/j.1365-2044.1990.tb14683.x. PMID 2334030. S2CID 28358731.
^ ^a ^b ^c ^d Reddy DS (2003). "Pharmacology of endogenous neuroactive steroids". Crit Rev Neurobiol. 15 (3–4): 197–234. doi:10.1615/critrevneurobiol.v15.i34.20. PMID 15248811.
^ ^a ^b ^c Jürgen Schüttler; Helmut Schwilden (8 January 2008). Modern Anesthetics. Springer Science & Business Media. pp. 278–. ISBN 978-3-540-74806-9.
^ Mellor DJ, Diesch TJ, Gunn AJ, Bennet L (2005). "The importance of 'awareness' for understanding fetal pain". Brain Res. Brain Res. Rev. 49 (3): 455–71. doi:10.1016/j.brainresrev.2005.01.006. PMID 16269314. S2CID 9833426.
^ Lagercrantz H, Changeux JP (2009). "The emergence of human consciousness: from fetal to neonatal life". Pediatr. Res. 65 (3): 255–60. doi:10.1203/PDR.0b013e3181973b0d. PMID 19092726. S2CID 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).
^ Norman Calvey; Norton Williams (21 January 2009). Principles and Practice of Pharmacology for Anaesthetists. John Wiley & Sons. pp. 110–. ISBN 978-1-4051-9484-6.

[pmid7839787-1] ^ ^a ^b ^c ^d ^e ^f ^g Carl P, Høgskilde S, Lang-Jensen T, et al. (October 1994). "Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans". Acta Anaesthesiol Scand. 38 (7): 734–41. doi:10.1111/j.1399-6576.1994.tb03987.x. PMID 7839787. S2CID 22005284.

[pmid1547051-2] Gray HS, Holt BL, Whitaker DK, Eadsforth P (March 1992). "Preliminary study of a pregnanolone emulsion (Kabi 2213) for i.v. induction of general anaesthesia". Br J Anaesth. 68 (3): 272–6. doi:10.1093/bja/68.3.272. PMID 1547051. S2CID 19193898.

[pmid2334030-3] Carl P, Høgskilde S, Nielsen JW, Sørensen MB, Lindholm M, Karlen B, Bäckstrøm T (March 1990). "Pregnanolone emulsion. A preliminary pharmacokinetic and pharmacodynamic study of a new intravenous anaesthetic agent". Anaesthesia. 45 (3): 189–97. doi:10.1111/j.1365-2044.1990.tb14683.x. PMID 2334030. S2CID 28358731.

[pmid15248811-4] Reddy DS (2003). "Pharmacology of endogenous neuroactive steroids". Crit Rev Neurobiol. 15 (3–4): 197–234. doi:10.1615/critrevneurobiol.v15.i34.20. PMID 15248811.

[SchüttlerSchwilden2008-5] Jürgen Schüttler; Helmut Schwilden (8 January 2008). Modern Anesthetics. Springer Science & Business Media. pp. 278–. ISBN 978-3-540-74806-9.

[pmid16269314-6] Mellor DJ, Diesch TJ, Gunn AJ, Bennet L (2005). "The importance of 'awareness' for understanding fetal pain". Brain Res. Brain Res. Rev. 49 (3): 455–71. doi:10.1016/j.brainresrev.2005.01.006. PMID 16269314. S2CID 9833426.

[pmid19092726-7] Lagercrantz H, Changeux JP (2009). "The emergence of human consciousness: from fetal to neonatal life". Pediatr. Res. 65 (3): 255–60. doi:10.1203/PDR.0b013e3181973b0d. PMID 19092726. S2CID 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).

[CalveyWilliams2009-8] Norman Calvey; Norton Williams (21 January 2009). Principles and Practice of Pharmacology for Anaesthetists. John Wiley & Sons. pp. 110–. ISBN 978-1-4051-9484-6.

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