From Wikipedia, the free encyclopedia
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 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
GABAA 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 (
INN Tooltip 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 .
Ionotropic
GABAA Tooltip γ-Aminobutyric acid A receptor
Positive modulators (abridged; see
here 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 and
dihydropicrotoxinin )
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 constituents
Monoureides
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 and
picrotoxinin )
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