ELTANOLONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H34O2
Molecular Weight	318.4935
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CC[C@]4([H])C[C@H](O)CC[C@]34C

InChI

InChIKey=AURFZBICLPNKBZ-YZRLXODZSA-N

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

HIDE SMILES / InChI

Molecular Formula	C21H34O2
Molecular Weight	318.4935
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 8
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15248811 | https://www.ncbi.nlm.nih.gov/pubmed/7839787 | https://www.ncbi.nlm.nih.gov/pubmed/25117207 | https://www.ncbi.nlm.nih.gov/pubmed/15033889 | 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 | https://clinicaltrials.gov/ct2/show/NCT01336413

Eltanolone (pregnanolone) is an endogenous neuro active steroid that is biosynthesized from progesterone. It is a positive allosteric modulator of the GABAA receptor, as well as a negative allosteric modulator of the glycine receptor. There is strong evidence that it is involved in the pathophysiology of premenstrual syndrome, catamenial epilepsy, major depression, and stress-sensitive brain disorders and is known to have sedative, anxiolytic, anesthetic, and anticonvulsant effects. It was investigated for clinical use as a general (intravenous) anesthetic. It produced unwanted side effects such as convulsions on occasion, and for that reason was not marketed. Pregnanolone possesses neuroprotective and neurotrophic properties thus has been through a number of clinical trials including for treatment of traumatic brain injury (TBI), Alzheimer disease, cognitive impairment and fragile X-associated tremor/ataxia syndrome.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA A receptor alpha-1/beta-1/gamma-2 7 Target ID: CHEMBL2111392 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15033889	Modulator 828		0.26 µM [EC50]
Glycine receptor 13 Target ID: CHEMBL3392921 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15033889	Modulator 828		0.25 µM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Brain injuries, traumatic 1 Sources: https://clinicaltrials.gov/ct2/show/NCT01336413	Primary	Phase II 1132	Unknown Approved Use Unknown
Alzheimer’s disease 272 Sources: https://clinicaltrials.gov/ct2/show/NCT02221622	Primary	Phase I 428	Unknown Approved Use Unknown
Mild cognitive impairment 5 Sources: https://clinicaltrials.gov/ct2/show/NCT02221622	Primary	Phase I 428	Unknown Approved Use Unknown
Fragile X-associated tremor/Ataxia syndrome 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02603926	Primary	Phase II 1132	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
163 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2334030	0.5 mg/kg 2 times / 4 weeks multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		ELTANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.26 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2334030	0.5 mg/kg 2 times / 4 weeks multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		ELTANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	UGT2B4 249 UGT2B7 389

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	yes
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	yes

PubMed

Title	Date	PubMed
Current perspectives on the role of neurosteroids in PMS and depression.	2001	11599311
Clinical implications of circulating neurosteroids.	2001	11599308
Synergistic protection of allopregnanolone and phenobarbital against maximal electroshock seizures in mice.	2001 Apr	11742590
Steroid structure and pharmacological properties determine the anti-amnesic effects of pregnenolone sulphate in the passive avoidance task in rats.	2001 Dec	11860495
The interaction between ethanol and pregnanolone at induction of anaesthesia investigated with a threshold method in male rats.	2001 Dec	11724744
Ventral tegmental area infusions of inhibitors of the biosynthesis and metabolism of 3alpha,5alpha-THP attenuate lordosis of hormone-primed and behavioural oestrous rats and hamsters.	2001 Dec	11722704
Diminished allopregnanolone enhancement of GABA(A) receptor currents in a rat model of chronic temporal lobe epilepsy.	2001 Dec 1	11731578
The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders.	2001 Nov	11744079
Role of allopregnanolone in regulation of GABA(A) receptor plasticity during long-term exposure to and withdrawal from progesterone.	2001 Nov	11744076
The negative GABA(A) modulator methyl beta-carboline-3-carboxylate attenuates the behavioral effects of the positive GABA(A) modulators triazolam and pregnanolone in rhesus monkeys.	2001 Nov	11713619
Influence of membrane cholesterol on modulation of the GABA(A) receptor by neuroactive steroids and other potentiators.	2001 Nov	11704651
Neuroactive steroids modulate crustacean locomotor activity.	2001 Nov 2	11684341
3Alpha-hydroxy-5alpha-pregnan-20-one levels and GABA(A) receptor-mediated 36Cl(-) flux across development in rat cerebral cortex.	2001 Nov 26	11718833
Neuroendocrine effects of raloxifene hydrochloride in postmenopausal women.	2001 Oct	11727358
Allopregnanolone and pentobarbital infused into the nucleus accumbens substitute for the discriminative stimulus effects of ethanol.	2001 Oct	11696663
Increased expression of the neuropeptide Y receptor Y(1) gene in the medial amygdala of transgenic mice induced by long-term treatment with progesterone or allopregnanolone.	2001 Oct	11677270
Pressure-sensitive and -insensitive coupling in gamma-aminobutyric acid(A) receptors.	2001 Oct	11605100
A rapid method for obtaining finasteride, a 5alpha-reductase inhibitor, from commercial tablets.	2002 Apr	12034332
Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines.	2002 Apr	11995921
Modulation Of [35S]-tert-butylbicyclophosphorothionate binding by somatostatin in rat hypothalamus.	2002 Apr	11985538
Two neuroactive steroids in midpregnancy as measured in maternal and fetal sera and in amniotic fluid.	2002 Apr	11958797
Homocysteine and steroids levels in metformin treated women with polycystic ovary syndrome.	2002 Apr	11928069
Depletion of cortical allopregnanolone potentiates stress-induced increase in cortical dopamine output.	2002 Apr 5	11911871
Neonatal isolation alters stress hormone and mesolimbic dopamine release in juvenile rats.	2002 Aug	12076726
Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture.	2002 Aug 2	12123853
Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone is influenced by common genes.	2002 Feb	11895174
Can molecular similarity-activity models for intravenous general anaesthetics help explain their mechanism of action?	2002 Feb	11878651
Increased response of plasma allopregnanolone to corticotropin-releasing hormone in obese patients.	2002 Feb	11867940
Inhibition of the NMDA response by pregnenolone sulphate reveals subtype selective modulation of NMDA receptors by sulphated steroids.	2002 Feb	11861317
GABA(A) receptor-modulating neuroactive steroid composition in patients with panic disorder before and during paroxetine treatment.	2002 Jan	11772707
Social isolation stress during the third week of life has age-dependent effects on spatial learning in rats.	2002 Jan 22	11796160
Initial sensitivity, tolerance and cross-tolerance to allopregnanolone- and ethanol-induced hypothermia in selected mouse lines.	2002 Jul	12122490
Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam.	2002 Jul	12062590
Reinforcing effects of the neurosteroid allopregnanolone in rats.	2002 Jul	12062582
Effect of allopregnanolone on d-[3H]-aspartate release and [3H]-glutamate uptake in the hippocampus of kainate-treated mice.	2002 Jun	12120899
Prevention of the stress-induced increase in the concentration of neuroactive steroids in rat brain by long-term administration of mirtazapine but not of fluoxetine.	2002 Jun	12095071
Discriminative stimulus effects of ethanol in C57BL/6J and DBA/2J inbred mice.	2002 Jun	12068241
Effect of centrally injected allopregnanolone on sexual receptivity, luteinizing hormone release, hypothalamic dopamine turnover, and release in female rats.	2002 Mar	12041918
Changes in GABAA receptor gamma 2 subunit gene expression induced by long-term administration of oral contraceptives in rats.	2002 Mar	11897111
Pulsatile secretory characteristics of allopregnanolone, a neuroactive steroid, during the menstrual cycle and in amenorrheic subjects.	2002 Mar	11888841
Daily treatment with diazepam differentially modifies sensitivity to the effects of gamma-aminobutyric acid(A) modulators on schedule-controlled responding in rhesus monkeys.	2002 Mar	11861811
The effects of the neuroactive steroid 3 alpha,5 alpha-THDOC on sleep in the rat.	2002 Mar 25	11930167
GABA(B) receptor-mediated increase of neurosteroids by gamma-hydroxybutyric acid.	2002 May	12015204
Effects of the new generation selective estrogen receptor modulator EM-652 and oral administration of estradiol valerate on circulating, brain, and adrenal beta-endorphin and allopregnanolone levels in intact fertile and ovariectomized rats.	2002 May	12009361
High serum allopregnanolone levels in girls with precocious puberty.	2002 May	11994373
The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one affects dopamine-mediated behavior in rodents.	2002 May	11981591
Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats.	2002 May	11971664
Withdrawal properties of a neuroactive steroid: implications for GABA(A) receptor gene regulation in the brain and anxiety behavior.	2002 May	11960630
Neuroactive steroid changes in response to challenge with the panicogenic agent pentagastrin.	2002 May	11911996
Allopregnanolone inhibits learning in the Morris water maze.	2002 May 3	11955475

Patents

Sample Use Guides

In Vivo Use Guide

Pregnenolone 50 mg BID for 14 days, followed by 150 mg BID for 14 days, followed by 250 mg BID x thereafter for the remainder of the 8-week trial

Route of Administration: Oral

In Vitro Use Guide

Cholesterol enrichment of the neurones, isolated from 10 to 16-day-old Wistar rat brains, was achieved by incubation with cholesterol + phosphatidylcholine liposomes. Cholesterol enrichment (25.8+/-3.4%) reduced the potentiation of GABA(A) currents by pregnanolone (0.3 and 1 uM). Acute application of cholesterol (1 uM) did not significantly change the potentiation of GABA(A) currents by pregnanolone (1 uM).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:29:39 GMT 2023` Edited by `admin` on `Fri Dec 15 15:29:39 GMT 2023`
Record UNII	BXO86P3XXW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ELTANOLONE

Official Name

English

NSC-82867

Code

English

ELTANOLONE [MART.]

Common Name

English

5.BETA.-PREGNAN-20-ONE, 3.ALPHA.-HYDROXY-

Systematic Name

English

KABI-2213

Code

English

SKF-6455

Code

English

eltanolone [INN]

Common Name

English

KABI 2213

Code

English

PREGNAN-3.ALPHA.-OL-20-ONE [MI]

Common Name

English

PREGNANOLONE

Common Name

English

PREGNAN-20-ONE, 3-HYDROXY-, (3.ALPHA.,5.BETA.)-

Systematic Name

English

3.ALPHA.-HYDROXY-5.BETA.-PREGNAN-20-ONE

Systematic Name

English

Classification Tree Code System Code

LOINC

83132-1