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This article is about the 3α,5β-reduced metabolite of progesterone. For other pregnanolone isomers of progesterone, see
Pregnanolone (disambiguation) .
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
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
100.162.192
UNII
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
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
C 21 H 34 O 2
Molar mass
318.501 g·mol−1
Pharmacology
Intravenous injection [1]
Pharmacokinetics :
0.9–3.5 hours[1] [2] [3]
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Pregnanolone ,also known aseltanolone ,is anendogenous inhibitory neurosteroid which is produced in the body fromprogesterone .[4] It is closely related toallopregnanolone ,which has similar properties.[4]
Biological activity [ edit ]
Pregnanolone is apositive allosteric modulator of theGABAA receptor ,[4] as well as anegative allosteric modulator of theglycine receptor .[5]
Biological function [ edit ]
Pregnanolone hassedative ,anxiolytic ,anesthetic ,andanticonvulsant effects.[4] [5] [1] Duringpregnancy ,pregnanolone andallopregnanolone are involved insedation andanesthesia of thefetus .[6] [7]
Biochemistry [ edit ]
Pregnanolone is synthesized fromprogesterone via theenzymes 5β-reductase and3α-hydroxysteroid dehydrogenase ,with5β-dihydroprogesterone occurring as ametabolic intermediate .Theelimination half-life of pregnanolone is between 0.9 and 3.5 hours.[1] [2] [3]
Chemistry [ edit ]
Pregnanolone, also known as 3α,5β-tetrahydroprogesterone (3α,5β-THP) or as 5β-pregnan-3α-ol-20-one, is anaturally occurring pregnane steroid and aderivative ofprogesterone .Related compounds includeallopregnanolone (3α,5α-THP; brexanolone),epipregnanolone (3β,5β-THP),hydroxydione ,isopregnanolone (3β,5α-THP), andrenanolone .
History [ edit ]
Pregnanolone was first isolated from theurine of pregnant women in 1937.[1] Its anesthetic properties were first demonstrated in animals in 1957.[1]
Research [ edit ]
Pregnanolone was investigated for clinical use as ageneral anesthetic under the nameeltanolone (INN Tooltip International Nonproprietary Name ), but produced unwantedside effects such asconvulsions on occasion, and for this reason, was never marketed.[5] [8] [1]
References [ edit ]
^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 .
Ionotropic
GABAA Tooltip γ-Aminobutyric acid A receptor
Positive modulators (abridged; seehere for a full list): α-EMTBL
Alcohols (e.g.,drinking alcohol ,2M2B )
Anabolic steroids
Avermectins (e.g.,ivermectin )
Barbiturates (e.g.,phenobarbital )
Benzodiazepines (e.g.,diazepam )
Bromide compounds (e.g.,potassium bromide )
Carbamates (e.g.,meprobamate )
Carbamazepine
Chloralose
Chlormezanone
Clomethiazole
Dihydroergolines (e.g.,ergoloid (dihydroergotoxine) )
Etazepine
Etifoxine
Fenamates (e.g.,mefenamic acid )
Flavonoids (e.g.,apigenin ,hispidulin )
Fluoxetine
Flupirtine
Imidazoles (e.g.,etomidate )
Kava constituents (e.g.,kavain )
Lanthanum
Loreclezole
Monastrol
Neuroactive steroids (e.g.,allopregnanolone ,cholesterol ,THDOC )
Niacin
Niacinamide
Nonbenzodiazepines (e.g.,β-carbolines (e.g.,abecarnil ),cyclopyrrolones (e.g.,zopiclone ),imidazopyridines (e.g.,zolpidem ),pyrazolopyrimidines (e.g.,zaleplon ))
Norfluoxetine
Petrichloral
Phenols (e.g.,propofol )
Phenytoin
Piperidinediones (e.g.,glutethimide )
Propanidid
Pyrazolopyridines (e.g.,etazolate )
Quinazolinones (e.g.,methaqualone )
Retigabine (ezogabine)
ROD-188
Skullcap constituents (e.g.,baicalin )
Stiripentol
Sulfonylalkanes (e.g.,sulfonmethane (sulfonal) )
Topiramate
Valerian constituents (e.g.,valerenic acid )
Volatiles /gases (e.g.,chloral hydrate ,chloroform ,diethyl ether ,paraldehyde ,sevoflurane )
Negative modulators: 1,3M1B
3M2B
11-Ketoprogesterone
17-Phenylandrostenol
α3IA
α5IA (LS-193,268)
β-CCB
β-CCE
β-CCM
β-CCP
β-EMGBL
Anabolic steroids
Amiloride
Anisatin
β-Lactams (e.g.,penicillins ,cephalosporins ,carbapenems )
Basmisanil
Bemegride
Bicyclic phosphates (TBPS ,TBPO ,IPTBO )
BIDN
Bilobalide
Bupropion
CHEB
Chlorophenylsilatrane
Cicutoxin
Cloflubicyne
Cyclothiazide
DHEA
DHEA-S
Dieldrin
(+)-DMBB
DMCM
DMPC
EBOB
Etbicyphat
FG-7142 (ZK-31906)
Fiproles (e.g.,fipronil )
Flavonoids (e.g.,amentoflavone ,oroxylin A )
Flumazenil
Fluoroquinolones (e.g.,ciprofloxacin )
Flurothyl
Furosemide
Golexanolone
Iomazenil (123 I)
IPTBO
Isopregnanolone (sepranolone)
L-655,708
Laudanosine
Lindane
MaxiPost
Morphine
Morphine-3-glucuronide
MRK-016
Naloxone
Naltrexone
Nicardipine
Nonsteroidal antiandrogens (e.g.,apalutamide ,bicalutamide ,enzalutamide ,flutamide ,nilutamide )
Oenanthotoxin
Pentylenetetrazol (pentetrazol)
Phenylsilatrane
Picrotoxin (i.e.,picrotin ,picrotoxinin anddihydropicrotoxinin )
Pregnenolone sulfate
Propybicyphat
PWZ-029
Radequinil
Ro 15-4513
Ro 19-4603
RO4882224
RO4938581
Sarmazenil
SCS
Suritozole
TB-21007
TBOB
TBPS
TCS-1105
Terbequinil
TETS
Thujone
U-93631
Zinc
ZK-93426
GABAA -ρ Tooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
GABAB Tooltip γ-Aminobutyric acid B receptor
Alcohols Barbiturates Benzodiazepines Carbamates Flavonoids Imidazoles Kava constituentsMonoureides Neuroactive steroids Nonbenzodiazepines Phenols Piperidinediones Pyrazolopyridines Quinazolinones Volatiles /gases Others/unsorted
3-Hydroxybutanal
α-EMTBL
AA-29504
Alogabat
Avermectins (e.g.,ivermectin )
Bromide compounds (e.g.,lithium bromide ,potassium bromide ,sodium bromide )
Carbamazepine
Chloralose
Chlormezanone
Clomethiazole
Darigabat
DEABL
Deuterated etifoxine
Dihydroergolines (e.g.,dihydroergocryptine ,dihydroergosine ,dihydroergotamine ,ergoloid (dihydroergotoxine) )
DS2
Efavirenz
Etazepine
Etifoxine
Fenamates (e.g.,flufenamic acid ,mefenamic acid ,niflumic acid ,tolfenamic acid )
Fluoxetine
Flupirtine
Hopantenic acid
KRM-II-81
Lanthanum
Lavender oil
Lignans (e.g.,4-O-methylhonokiol ,honokiol ,magnolol ,obovatol )
Loreclezole
Menthyl isovalerate (validolum)
Monastrol
Niacin
Niacinamide
Org 25,435
Phenytoin
Propanidid
Retigabine (ezogabine)
Safranal
Seproxetine
Stiripentol
Sulfonylalkanes (e.g.,sulfonmethane (sulfonal) ,tetronal ,trional )
Terpenoids (e.g.,borneol )
Topiramate
Valerian constituents (e.g.,isovaleric acid ,isovaleramide ,valerenic acid ,valerenol )
Receptor (ligands )
GlyR Tooltip Glycine receptor
Positive modulators: Alcohols (e.g.,brometone ,chlorobutanol (chloretone) ,ethanol (alcohol) ,tert -butanol (2M2P) ,tribromoethanol ,trichloroethanol ,trifluoroethanol )
Alkylbenzene sulfonate
Anandamide
Barbiturates (e.g.,pentobarbital ,sodium thiopental )
Chlormethiazole
D12-116
Dihydropyridines (e.g.,nicardipine )
Etomidate
Ginseng constituents (e.g.,ginsenosides (e.g.,ginsenoside-Rf ))
Glutamic acid (glutamate)
Ivermectin
Ketamine
Neuroactive steroids (e.g.,alfaxolone ,pregnenolone (eltanolone) ,pregnenolone acetate ,minaxolone ,ORG-20599 )
Nitrous oxide
Penicillin G
Propofol
Tamoxifen
Tetrahydrocannabinol
Triclofos
Tropeines (e.g.,atropine ,bemesetron ,cocaine ,LY-278584 ,tropisetron ,zatosetron )
Volatiles /gases (e.g.,chloral hydrate ,chloroform ,desflurane ,diethyl ether (ether) ,enflurane ,halothane ,isoflurane ,methoxyflurane ,sevoflurane ,toluene ,trichloroethane (methyl chloroform) ,trichloroethylene )
Xenon
Zinc
Antagonists: 2-Aminostrychnine
2-Nitrostrychnine
4-Phenyl-4-formyl-N-methylpiperidine
αEMBTL
Bicuculline
Brucine
Cacotheline
Caffeine
Colchicine
Colubrine
Cyanotriphenylborate
Dendrobine
Diaboline
Endocannabinoids (e.g.,2-AG ,anandamide (AEA) )
Gaboxadol (THIP)
Gelsemine
iso-THAZ
Isobutyric acid
Isonipecotic acid
Isostrychnine
Laudanosine
N-Methylbicuculline
N-Methylstrychnine
N,N-Dimethylmuscimol
Nipecotic acid
Pitrazepin
Pseudostrychnine
Quinolines (e.g.,4-hydroxyquinoline ,4-hydroxyquinoline-3-carboxylic acid ,5,7-CIQA ,7-CIQ ,7-TFQ ,7-TFQA )
RU-5135
Sinomenine
Strychnine
Thiocolchicoside
Tutin
Negative modulators: Amiloride
Benzodiazepines (e.g.,bromazepam ,clonazepam ,diazepam ,flunitrazepam ,flurazepam )
Corymine
Cyanotriphenylborate
Daidzein
Dihydropyridines (e.g.,nicardipine ,nifedipine ,nitrendipine )
Furosemide
Genistein
Ginkgo constituents (e.g.,bilobalide ,ginkgolides (e.g.,ginkgolide A ,ginkgolide B ,ginkgolide C ,ginkgolide J ,ginkgolide M ))
Imipramine
NBQX
Neuroactive steroids (e.g.,3α-androsterone sulfate ,3β-androsterone sulfate ,deoxycorticosterone ,DHEA sulfate ,pregnenolone sulfate ,progesterone )
Opioids (e.g.,codeine ,dextromethorphan ,dextrorphan ,levomethadone ,levorphanol ,morphine ,oripavine ,pethidine ,thebaine )
Picrotoxin (i.e.,picrotin andpicrotoxinin )
PMBA
Riluzole
Tropeines (e.g.,bemesetron ,LY-278584 ,tropisetron ,zatosetron )
Verapamil
Zinc
NMDAR Tooltip N-Methyl-D-aspartate receptor
Transporter (blockers )
GlyT1 Tooltip Glycine transporter 1 GlyT2 Tooltip Glycine transporter 2
CAR Tooltip Constitutive androstane receptor PXR Tooltip Pregnane X receptor