GABOXADOL MONOHYDRATE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H8N2O2.H2O
Molecular Weight	158.1552
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.OC1=NOC2=C1CCNC2

InChI

InChIKey=UDHPXYNRXFPDOF-UHFFFAOYSA-N

InChI=1S/C6H8N2O2.H2O/c9-6-4-1-2-7-3-5(4)10-8-6;/h7H,1-3H2,(H,8,9);1H2

HIDE SMILES / InChI

Molecular Formula	C6H8N2O2
Molecular Weight	140.1399
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28993837 | https://harpers.org/archive/2013/08/gaboxadol/5/ | https://www.ncbi.nlm.nih.gov/pubmed/15451401 | http://www.ovidrx.com/our-pipeline/

Gaboxadol (or THIP) is a direct GABA mimetic ligand at delta-containing receptors. Gaboxadol went into human clinical trials to test if the drug promoted sleep. It was generally well tolerated. Gaboxadol enhances delta power in NREM sleep in humans. Gaboxadol failed in Phase III for sleep studies. The side effects of Gaboxadol have been described as mild and similar in quality to those of other GABA-mimetics. Gaboxadol is in development with Ovid Therapeutics as a treatment for Angelman syndrome, fragile X syndrome and epilepsy.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 203 Target ID: CHEMBL2093872 Sources: http://adisinsight.springer.com/drugs/800014543 \| https://www.ncbi.nlm.nih.gov/pubmed/28993837 \| http://www.ovidrx.com/our-pipeline/	Agonist 2752

Conditions

Condition	Modality	Highest Phase	Product
Insomnia 111 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22057018 https://www.ncbi.nlm.nih.gov/pubmed/22003345	Primary	Phase III 665	Unknown Approved Use Unknown
Major depressive disorder 179 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22008735	Primary	Phase II 1147	Unknown Approved Use Unknown
Angelman syndrome 4 Sources: http://www.ovidrx.com/our-pipeline/	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
123 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19094161	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		GABOXADOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
147 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19094161	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		GABOXADOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
408 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19094161	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		GABOXADOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
440 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19094161	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		GABOXADOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19094161	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		GABOXADOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19094161	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		GABOXADOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
10 mg single, oral Studied dose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19094161	healthy Health Status: healthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19094161	Disc. AE: Vasovagal reaction, vomiting... AEs leading to discontinuation/dose reduction: Vasovagal reaction (1 pt) vomiting (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19094161
15 mg 1 times / day multiple, oral Studied dose Dose: 15 mg, 1 times / day Route: oral Route: multiple Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19346160	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19346160	Disc. AE: headache, Dizziness... AEs leading to discontinuation/dose reduction: headache (9.2%) Dizziness (9.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/19346160

AEs

AE	Significance	Dose	Population
Vasovagal reaction	1 pt Disc. AE	10 mg single, oral Studied dose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19094161	healthy Health Status: healthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19094161
vomiting	1 pt Disc. AE	10 mg single, oral Studied dose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19094161	healthy Health Status: healthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19094161
Dizziness	9.2% Disc. AE	15 mg 1 times / day multiple, oral Studied dose Dose: 15 mg, 1 times / day Route: oral Route: multiple Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19346160	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19346160
headache	9.2% Disc. AE	15 mg 1 times / day multiple, oral Studied dose Dose: 15 mg, 1 times / day Route: oral Route: multiple Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19346160	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19346160

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003R6A	https://www.1pchem.com/search?query=1P003R6A
1PlusChem LLC	1P006TKI	https://www.1pchem.com/search?query=1P006TKI
A2B Chem	AB74386	http://a2bchem.com/prod/AB74386
AA Blocks	AA003QMU	http://aablocks.com/goods/Goods/detail?id=AA003QMU
AK Scientific	7955AL	https://aksci.com/item_detail.php?cat=7955AL
Alfa Chemistry	85118-33-8	http://www.alfa-chemistry.com/search.aspx?q=85118-33-8
ApexBio Technology	B6460	https://www.apexbt.com/catalogsearch/result/?q=B6460
AstaTech	P17040	http://astatechinc.com/CPSResult.php?CRNO=P17040
BOC Sciences	64603-91-4	http://www.bocsci.com/description.asp?cas=64603-91-4
Cayman Chemical	16355	http://www.caymanchem.com/app/template/Product.vm/catalog/16355
Chem Scene	CS-0002508	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0002508
Chemspace	CSC000065342	https://chem-space.com/CSC000065342
Chemspace	CSC015310339	https://chem-space.com/CSC015310339
eMolecules	300000141	https://orderbb.emolecules.com/search/#?query=300000141
eMolecules	300575231	https://orderbb.emolecules.com/search/#?query=300575231
eMolecules	42682706	https://orderbb.emolecules.com/search/#?query=42682706
eMolecules	50577872	https://orderbb.emolecules.com/search/#?query=50577872
eMolecules	93433782	https://orderbb.emolecules.com/search/#?query=93433782
Enamine	BBV-38271272	http://www.enaminestore.com/catalog/BBV-38271272
Enamine	BBV-38393882	http://www.enaminestore.com/catalog/BBV-38393882
Enamine	EN300-152453	https://www.enaminestore.com/catalog/EN300-152453
eNovation Chemicals	D767308	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D767308&searchbtn.x=0&searchbtn.y=0
Fluorochem	535017	http://www.fluorochem.co.uk/Products/Product?code=535017
KeyOrganics	AS-53745	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-53745
Lab Network	LN01296249	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01296249
mcule	MCULE-8440237252	https://mcule.com/MCULE-8440237252/
MedChem Express	HY-10233	https://www.medchemexpress.com/search.html?q=HY-10233&ft=&fa=&fp=
MolPort	MolPort-003-666-496	https://www.molport.com/shop/molecule-link/MolPort-003-666-496
MolPort	MolPort-006-141-665	https://www.molport.com/shop/molecule-link/MolPort-006-141-665
MuseChem	R042364	https://www.musechem.com/product/R042364.html
Princeton BioMolecular Research	PBMR221636	http://www.princetonbio.com/order_online?common_id=PBMR221636
ShangHai Biochempartner	BCP07031	http://www.biochempartner.com/search_BCP07031
ShangHai Biochempartner	BCP16610	http://www.biochempartner.com/search_BCP16610
Tocris	807	https://www.tocris.com/search.php?Type=QuickSearch&Value=0807
Toronto Research Chemicals	C432755	https://www.trc-canada.com/product-detail/?CatNum=C432755
Toronto Research Chemicals	KIT1240	https://www.trc-canada.com/product-detail/?CatNum=KIT1240

PubMed

Title	Date	PubMed
Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats.	2008-05	18264695
Efficacy of the selective extrasynaptic GABA A agonist, gaboxadol, in a model of transient insomnia: a randomized, controlled clinical trial.	2008-05	17765013
Enhanced behavioral sensitivity to the competitive GABA agonist, gaboxadol, in transgenic mice over-expressing hippocampal extrasynaptic alpha6beta GABA(A) receptors.	2008-04	18021290
The role of GABA(A) receptors in the control of transient lower oesophageal sphincter relaxations in the dog.	2008-03	18204479
The expression of GABAA beta subunit isoforms in synaptic and extrasynaptic receptor populations of mouse dentate gyrus granule cells.	2008-02-15	18079158
[New hypnotics: perspectives from sleep physiology].	2008-02-13	18265473
Functional consequences of GABAA receptor alpha 4 subunit deletion on synaptic and extrasynaptic currents in mouse dentate granule cells.	2008-01	18070250
Identification of a domain in the delta subunit (S238-V264) of the alpha4beta3delta GABAA receptor that confers high agonist sensitivity.	2007-11	17711419
GABAergic modulation of binge-like ethanol intake in C57BL/6J mice.	2007-11	17698181
Short-term treatment with gaboxadol improves sleep maintenance and enhances slow wave sleep in adult patients with primary insomnia.	2007-11	17653697
Development and validation of a selective and sensitive bioanalytical procedure for the quantitative determination of gaboxadol in human plasma employing mixed mode solid phase extraction and hydrophilic interaction liquid chromatography with tandem mass spectroscopic detection.	2007-10-15	17851145
Neurochemical regulation of sleep.	2007-10	16777143
Postnatal development and kinetics of [3H]gaboxadol binding in rat brain: in vitro homogenate binding and quantitative autoradiography.	2007-09-19	17692833
Flumazenil selectively prevents the increase in alpha(4)-subunit gene expression and an associated change in GABA(A) receptor function induced by ethanol withdrawal.	2007-08	17403139
Dual GABAA receptor-mediated inhibition in rat presympathetic paraventricular nucleus neurons.	2007-07-15	17495040
New perspectives for the treatment of disorders of sleep and arousal.	2007-07	17652996
Lack of generalisation between the GABAA receptor agonist, gaboxadol, and allosteric modulators of the benzodiazepine binding site in the rat drug discrimination procedure.	2007-07	17361395
The importance of genetic background on pain behaviours and pharmacological sensitivity in the rat spared serve injury model of peripheral neuropathic pain.	2007-06-14	17383631
Plasma and CNS concentrations of Gaboxadol in rats following subcutaneous administration.	2007-05-07	17362924
The selective extrasynaptic GABAA agonist, gaboxadol, improves traditional hypnotic efficacy measures and enhances slow wave activity in a model of transient insomnia.	2007-05	17552374
GABAA receptors in the thalamus: alpha4 subunit expression and alcohol sensitivity.	2007-05	17521848
KCC2-deficient mice show reduced sensitivity to diazepam, but normal alcohol-induced motor impairment, gaboxadol-induced sedation, and neurosteroid-induced hypnosis.	2007-04	16936706
Gateways to clinical trials.	2007-03-09	17344945
Effect of short-term treatment with gaboxadol on sleep maintenance and initiation in patients with primary insomnia.	2007-03	17425224
The EEG effects of THIP (Gaboxadol) on sleep and waking are mediated by the GABA(A)delta-subunit-containing receptors.	2007-03	17408425
Gaboxadol, a selective extrasynaptic GABA(A) agonist, does not generalise to other sleep-enhancing drugs: a rat drug discrimination study.	2007-03	17196996
Auto-modulation of neuroactive steroids on GABA A receptors: a novel pharmacological effect.	2007-02	17084864
The progesterone metabolite allopregnanolone potentiates GABA(A) receptor-mediated inhibition of 5-HT neuronal activity.	2007-01-15	16574382
Mechanisms of sleep induction by GABA(A) receptor agonists.	2007	17539703
Treating insomnia: Current and investigational pharmacological approaches.	2006-12	16876255
Gateways to clinical trials.	2006-10	17136234
Deletion of the GABA(A) receptor alpha1 subunit increases tonic GABA(A) receptor current: a role for GABA uptake transporters.	2006-09-06	16957088
THIP, a hypnotic and antinociceptive drug, enhances an extrasynaptic GABAA receptor-mediated conductance in mouse neocortex.	2006-08	16221925
delta-Subunit containing GABAA receptor knockout mice are less sensitive to the actions of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol.	2006-07-17	16777089
Steroid withdrawal in the mouse results in anxiogenic effects of 3alpha,5beta-THP: a possible model of premenstrual dysphoric disorder.	2006-06	16193334
Discriminative stimulus effects of flumazenil: perceptual masking by baclofen, and lack of substitution with gamma-hydroxybutyrate and its precursors 1,4-butanediol and gamma-butyrolactone.	2006-05	16572002
Sleep circuitry and the hypnotic mechanism of GABAA drugs.	2006-04-15	17557503
Extrasynaptic GABAA receptors are critical targets for sedative-hypnotic drugs.	2006-04-15	17557502
Pharmacological characterisation of place escape/avoidance behaviour in the rat chronic constriction injury model of neuropathic pain.	2006-04	16479373
Pharmacological characterization of agonists at delta-containing GABAA receptors: Functional selectivity for extrasynaptic receptors is dependent on the absence of gamma2.	2006-03	16272218
Potent 4-arylalkyl-substituted 3-isothiazolol GABA(A) competitive/noncompetitive antagonists: synthesis and pharmacology.	2006-02-23	16480274
Involvement of GABAergic modulation of antinociception induced by morphine microinjected into the ventrolateral orbital cortex.	2006-02-16	16448630
Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptors.	2006-02-08	16467523
Gaboxadol--a new awakening in sleep.	2006-02	16368265
Impact of epsilon and theta subunits on pharmacological properties of alpha3beta1 GABAA receptors expressed in Xenopus oocytes.	2006-01-13	16412217
GABAA receptor-mediated tonic inhibition in thalamic neurons.	2005-12-14	16354913
An extrasynaptic GABAA receptor mediates tonic inhibition in thalamic VB neurons.	2005-12	16162835
Gateways to clinical trials.	2005-11	16357953
Gateways to clinical trials.	2005-06	16082422
Sleep disturbances, psychiatric disorders, and psychotropic drugs.	2005	16416708

Patents

Sample Use Guides

In Vivo Use Guide

5 or 10 mg once daily before bedtime for 8 weeks

Route of Administration: Oral

In Vitro Use Guide

In recombinant experiments it was found that δ subunit coexpression leads to receptors activated by nanomolar THIP concentrations (EC(50) of 30-50 nM for α4β3δ and α6β3δ), a sensitivity almost 1,000-fold higher than receptors formed by α4/6 and β3 subunits. In contrast, γ2 subunit expression significantly reduces THIP sensitivity.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:35:48 GMT 2025` Edited by `admin` on `Mon Mar 31 17:35:48 GMT 2025`
Record UNII	91413J4SLI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GABOXADOL MONOHYDRATE

Common Name

English

SOXAZOLO(5,4-C)PYRIDIN-3(2H)-ONE, 4,5,6,7-TETRAHYDRO-, HYDRATE (1:1)

Preferred Name

English

Code System Code Type Description

FDA UNII

91413J4SLI