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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H36O2
Molecular Weight 332.52
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GANAXOLONE

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@](C)(O)CC[C@]34C

InChI

InChIKey=PGTVWKLGGCQMBR-FLBATMFCSA-N
InChI=1S/C22H36O2/c1-14(23)17-7-8-18-16-6-5-15-13-20(2,24)11-12-21(15,3)19(16)9-10-22(17,18)4/h15-19,24H,5-13H2,1-4H3/t15-,16-,17+,18-,19-,20+,21-,22+/m0/s1

HIDE SMILES / InChI

Molecular Formula C22H36O2
Molecular Weight 332.52
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) (GNX) is the 3beta-methylated synthetic analog of allopregnanolone; it belongs to a class of compounds referred to as neurosteroids. GNX is an allosteric modulator of GABA(A) receptors acting through binding sites which are distinct from the benzodiazepine binding site. It has activity in a broad range of animal models of epilepsy. GNX has been shown to be well tolerated in adults and children. In early phase II studies, GNX has been shown to have activity in adult patients with partial-onset seizures and epileptic children with history of infantile spasms. It is currently undergoing further development in infants with newly diagnosed infantile spasms, in women with catamenial epilepsy, and in adults with refractory partial-onset seizures. Ganaxolone is a CNS-selective GABAA modulator being developed in three different dose forms (IV, capsule, and liquid) intended to maximize therapeutic reach to adult and pediatric patients in both acute and chronic care settings.Ganaxolone is a synthetic analog of endogenous allopregnanolone, which has been shown to be an effective anticonvulsant by restoring electrical balance to the seizing brain. While allopregnanolone’s anticonvulsant and anti-anxiety activities are well documented, allopregnanolone has the potential to convert back to its metabolic precursor progesterone, which could lead to hormonal side effects. Ganaxolone has been designed with an added methyl group that prevents back conversion to an active steroid which unlocks ganaxolone’s potential for chronic use. In preclinical studies, ganaxolone exhibited potency and efficacy comparable to allopregnanolone. Both ganaxolone and allopregnanolone bind to GABAA at the synaptic and extrasynaptic binding sites. Activity with extrasynaptic GABAA receptors are of particular importance for treating patients who developed tolerance to benzodiazepines and barbiturates. Ganaxolone binds to the GABAA receptors, which opens the pore to allow chloride ions to move into the postsynaptic neuron, leading to the inhibition of neurotransmission.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
106.23 ng/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
32.34 ng/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
376.03 ng/mL
500 mg 1 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
130 ng/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1093.13 ng × h/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
235.53 ng × h/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3103.04 ng × h/mL
500 mg 1 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
668 ng × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
65.1 h
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
37.7 h
500 mg 1 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
6.1 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GANAXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
36 mg/kg 1 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 36 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 36 mg/kg, 1 times / day
Sources:
unhealthy, CHILD
n = 20
Health Status: unhealthy
Condition: spasms syndrom
Age Group: CHILD
Sex: M+F
Food Status: UNKNOWN
Population Size: 20
Sources:
Disc. AE: Leukopenia...
AEs leading to
discontinuation/dose reduction:
Leukopenia (mild, 1 pt)
Sources:
1500 mg 1 times / day multiple, oral (unknown)
Studied dose
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Sources:
unhealthy
n = 98
Health Status: unhealthy
Condition: seizures
Sex: M+F
Food Status: UNKNOWN
Population Size: 98
Sources:
Disc. AE: rash...
AEs leading to
discontinuation/dose reduction:
rash (4.1%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Leukopenia mild, 1 pt
Disc. AE
36 mg/kg 1 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 36 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 36 mg/kg, 1 times / day
Sources:
unhealthy, CHILD
n = 20
Health Status: unhealthy
Condition: spasms syndrom
Age Group: CHILD
Sex: M+F
Food Status: UNKNOWN
Population Size: 20
Sources:
rash 4.1%
Disc. AE
1500 mg 1 times / day multiple, oral (unknown)
Studied dose
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Sources:
unhealthy
n = 98
Health Status: unhealthy
Condition: seizures
Sex: M+F
Food Status: UNKNOWN
Population Size: 98
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Anticonvulsant and behavioral effects of neuroactive steroids alone and in conjunction with diazepam.
1997 Aug
Future prospects for the drug treatment of epilepsy.
2001
The new generation of GABA enhancers. Potential in the treatment of epilepsy.
2001
A high-performance liquid chromatography-tandem mass spectrometric method for the determination of pharmacokinetics of ganaxolone in rat, monkey, dog and human plasma.
2001 Feb 10
Early postnatal ethanol intubation blunts GABA(A) receptor up-regulation and modifies 3alpha-hydroxy-5alpha-pregnan-20-one sensitivity in rat MS/DB neurons.
2001 Sep 23
Neurosteroids and infantile spasms: the deoxycorticosterone hypothesis.
2002
Changes in GABA(A) receptor gene expression induced by withdrawal of, but not by long-term exposure to, ganaxolone in cultured rat cerebellar granule cells.
2002 Dec
Newer GABAergic agents for pharmacotherapy of infantile spasms.
2002 Oct
Pharmacology of endogenous neuroactive steroids.
2003
Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice.
2003 Aug 8
The contraceptive agent Provera enhances GABA(A) receptor-mediated inhibitory neurotransmission in the rat hippocampus: evidence for endogenous neurosteroids?
2003 Nov 5
Catamenial epilepsy: pathophysiology, diagnosis, and management.
2003 Sep 1
Role of neurosteroids in catamenial epilepsy.
2004 Dec
Allopregnanolone analogs that positively modulate GABA receptors protect against partial seizures induced by 6-Hz electrical stimulation in mice.
2004 Jul
Pharmacology of catamenial epilepsy.
2004 Sep
[Perspectives of neurosteroid derivative application in antiepileptic therapy].
2005
Allopregnanolone and ganaxolone increase the firing activity of dorsal raphe nucleus serotonergic neurons in female rats.
2006 Apr
[A new aspect in the research on antiepileptic drugs].
2007 Feb
Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII).
2007 Jan
Treatment of Lennox-Gastaut syndrome: overview and recent findings.
2008 Dec
Modifications of antiepileptic drugs for improved tolerability and efficacy.
2008 Feb 14
Endogenous and synthetic neurosteroids in treatment of Niemann-Pick Type C disease.
2008 Mar
Current trends in the treatment of infantile spasms.
2009
Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX).
2009 Jan
Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions.
2009 Mar-Apr
Hormonal aspects of epilepsy.
2009 Nov
Neurosteroids: endogenous role in the human brain and therapeutic potentials.
2010
Anticonvulsant action of a new analogue of allopregnanolone in immature rats.
2010
Neurosteroids and epilepsy.
2010 Apr
"Epileptic encephalopathy" of infancy and childhood: electro-clinical pictures and recent understandings.
2010 Dec
Progress report on new antiepileptic drugs: a summary of the Tenth Eilat Conference (EILAT X).
2010 Dec
Anticonvulsant doses of ganaxolone do not compromise motor performance in immature rats.
2010 Jan 29
Patents

Sample Use Guides

200 mg and 225 mg capsules; target dose 1800 mg/day dosed 900mg 2x/day
Route of Administration: Oral
In Vitro Use Guide
Ganaxolone inhibited binding of the gamma-aminobutyric acid (GABA)A receptor-chloride channel ligand t-[35S]butylbicyclophosphorothionate (IC50 of 80 nM) and enhanced binding of the benzodiazepine site ligand [3H]flunitrazepam (EC50 of 125 nM) and the GABA site ligand [3H]muscimol (EC50 of 86 nM), consistent with activity as a positive allosteric modulator of the GABA(A) receptor. Electrophysiological recordings showed that, whereas nanomolar concentrations of ganaxolone potentiated GABA-evoked chloride currents in Xenopus oocytes expressing the human GABA(A) receptor subunits alpha1beta1gamma2L, alpha2beta1gamma2L or alpha3beta1gamma2L, direct activation of chloride flux occurred to a limited extent only at micromolar concentrations.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:35:38 GMT 2023
Edited
by admin
on Fri Dec 15 16:35:38 GMT 2023
Record UNII
98WI44OHIQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GANAXOLONE
INN   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
GANAXOLONE [MI]
Common Name English
3.ALPHA.-HYDROXY-3-METHYL-5.ALPHA.-PREGNAN-20-ONE
Systematic Name English
ZTALMY
Brand Name English
GANAXOLONE [USAN]
Common Name English
CCD1042
Code English
DEA NO. 2401
Code English
PREGNAN-20-ONE, 3-HYDROXY-3-METHYL-, (3.ALPHA.,5.ALPHA.)-
Common Name English
ganaxolone [INN]
Common Name English
3α-hydroxy-3β-methyl-5α-pregnan-20-one
Systematic Name English
CCD-1042
Code English
Ganaxolone [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 578017
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
FDA ORPHAN DRUG 473515
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
NCI_THESAURUS C265
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
FDA ORPHAN DRUG 489215
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
FDA ORPHAN DRUG 833521
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
DEA NO. 2401
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
FDA ORPHAN DRUG 547116
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
FDA ORPHAN DRUG 929822
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
FDA ORPHAN DRUG 81894
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
Code System Code Type Description
MERCK INDEX
m5662
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY Merck Index
PUBCHEM
6918305
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
RXCUI
2604689
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
EVMPD
SUB07880MIG
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
USAN
HH-6
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
EPA CompTox
DTXSID6046503
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
DRUG BANK
DB05087
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
INN
7476
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
DAILYMED
98WI44OHIQ
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
ChEMBL
CHEMBL1568698
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
SMS_ID
100000084535
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
NCI_THESAURUS
C72793
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
WIKIPEDIA
GANAXOLONE
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
CAS
38398-32-2
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
FDA UNII
98WI44OHIQ
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
MESH
C105051
Created by admin on Fri Dec 15 16:35:38 GMT 2023 , Edited by admin on Fri Dec 15 16:35:38 GMT 2023
PRIMARY
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