THIP (hydrobromid)
THIP (Gaboxadol) hydrobromide is a blood-brain barrier-penetrant, orally active selective GABAA receptor agonist. THIP hydrobromide exhibits EC50 values of 33 μM and 130 μM for α4β2δ and α4β1δ receptors, respectively. THIP hydrobromide activates extrasynaptic GABAA receptors to produce tonic inhibition and inhibits GABAergic interneurons to cause disinhibition. THIP hydrobromide is used in research on insomnia, sleep disorders, and addictive behaviors.
For research use only. We do not sell to patients.
- CAS No.: 65202-63-3
- Formula: C6H9BrN2O2
- Molecular Weight:221.05
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[3]|
α4β2δ 33 μM (EC50) |
α4β1δ 130 μM (EC50) |
In Vitro
THIP (Gaboxadol) (1-30 μM) hydrobromide induces tonic GABAA receptor-mediated currents in mouse neocortical layer 2/3 and layer 5 neurons (EC50 of 44 μM for layer 2/3 neurons), decreases inhibitory activity, and enhances excitatory activity[1].
THIP (0.34-7.0 mM; 20-120 min) hydrobromide exhibits transepithelial transport activity in Caco-2 cells[2].
THIP (up to 1000 μM; 15-90 min) hydrobromide exhibits uptake activity in rOat1-expressing Xenopus oocytes, with a Km of 151.2 μM and a Vmax of 0.78 pmol/oocyte/min[2].
THIP (1-10 mM) hydrobromide is a superagonist of α4β1δ, α4β2δ, and α4β3δ GABA-A receptors expressed in Xenopus oocytes, with EC50 values of 33 μM and 130 μM for α4β2δ and α4β3δ, respectively[3].
THIP (1 μM) hydrobromide decreases the frequency and amplitude of spontaneous GABAA receptor-mediated inhibitory postsynaptic currents (sIPSCs) in dopaminergic neurons of the ventral tegmental area (VTA) in mouse midbrain slices[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. .
Parmacokinetics
In Vivo
THIP (1-6 mg/kg; i.p.; single administration; observation from 1.5 h to 6 days) hydrobromide induces a transient decrease in spontaneous locomotor activity in Th-EGFP transgenic mice and C57BL/6J mice, and maintains long-lasting glutamate receptor plasticity in VTA dopaminergic neurons for an extended period after administration[5].
THIP (0.3-6 mg/kg; i.p.; once every other day for a total of 8 administrations over 4 sessions; 30 min per treatment) hydrobromide exhibits activity in inducing place aversion, without producing reward effects, in the conditioned place preference model in C57BL/6J mice[5].
THIP (0.1-3 mg/mL or 0.1-1.0 mg/kg/injection; intravenous injection; multiple administrations per day; single or 15 consecutive days) hydrobromide does not exhibit reinforcing or rewarding activity in intravenous self-administration models in adult male C57BL/6J mice and adult male olive baboons[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:GABA_A δ-subunit knockout (δ-/-) and wild-type littermate (δ+/+) on a mixed C57BL/6J × 129Sv/SvJ background (males and females; 11-13 weeks old; δ-/-: males 23.8 g, females 20.3 g; δ+/+: males 23.5 g, females 20.1 g)[4]
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Dosage:4 mg/kg, 6 mg/kg
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Administration:i.p.; single dose; recorded for 12 h
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Result:Induced an abnormal EEG pattern characterized by recurring spike-wave events in waking and NREM sleep in wild-type mice.
Significantly increased EEG power in the slow-wave activity (SWA) range for 2-3 hours in wild-type mice.
Lengthened REM sleep latency and suppressed REM sleep at the 6 mg/kg dose in wild-type mice.
Produced only minor, non-significant EEG changes in δ-subunit knockout mice.
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Animal Model:Papio hamadryas anubis (olive baboons, adult males)[5]
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Dosage:0.1, 0.18, 0.32, 1.0 mg/kg per injection
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Administration:i.v.; single dose; 15 days
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Result:No dose maintained a significantly greater rate of self-injection than did saline in any baboon (values to be exceeded were 3.4, 4.0, and 2.4 injections per day for baboons CR, HC, and SI, respectively).
Plasma concentrations increased dose-dependently and were highest at the time of the first sample, ~5 min after injection; values ranged from 0.53 to 1.24 μM (mean, 0.85 μM) at 0.1 mg/kg, from 3.1 to 4.3 μM (mean, 3.5 μM) at 0.32 mg/kg, and from 3.7 to 8.2 μM (mean, 5.4 μM) at 1.0 mg/kg.
Chemical Information
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CAS No. 65202-63-3
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Molecular Weight 221.05
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Formula C6H9BrN2O2
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SMILES
O=C1NOC2=C1CCNC2.Br
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Synonyms
Gaboxadol (hydrobromid)
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Drasbek KR, et al. THIP, a hypnotic and antinociceptive drug, enhances an extrasynaptic GABAA receptor-mediated conductance in mouse neocortex. Cerebral cortex (New York, N.Y. : 1991). 2006 Aug;16(8):1134-41. [Content Brief]
[2]. Larsen M, et al. 5-Hydroxy-L-tryptophan alters gaboxadol pharmacokinetics in rats: involvement of PAT1 and rOat1 in gaboxadol absorption and elimination. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2010 Jan 31;39(1-3):68-75. [Content Brief]
[3].
Hoestgaard-Jensen K, et
al. Probing α4βδ GABAA receptor heterogeneity: differential regional effects of a functionally selective α4β1δ/α4β3δ receptor agonist on tonic and phasic inhibition in rat brain. J Neurosci. 2014 Dec 3;34(49):16256-72.
[Content Brief]
[6]. Silverman NS, et al. Effects of gaboxadol on the expression of cocaine sensitization in rats. Experimental and clinical psychopharmacology. 2016 Apr;24(2):131-41. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
THIP (hydrobromid) Related Classifications
HY-10232A Related Classifications
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