THIP
Based on 1 publication(s) in Google Scholar
THIP (Gaboxadol) is a blood-brain barrier-penetrant, orally active selective GABAA receptor agonist. THIP exhibits EC50 values of 33 μM and 130 μM for α4β2δ and α4β1δ receptors, respectively. THIP activates extrasynaptic GABAA receptors to produce tonic inhibition and inhibits GABAergic interneurons to cause disinhibition. THIP is used in research on insomnia, sleep disorders, and addictive behaviors.
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- Purity : 99.89%
- CAS No.: 64603-91-4
- 화학식: C6H8N2O2
- 분자량:140.14
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) THIP
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Biological Activity
제품 설명
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.
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. 64603-91-4
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Appearance Solid
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분자량 140.14
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화학식 C6H8N2O2
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Color White to yellow
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SMILES
O=C1C2=C(CNCC2)ON1
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Synonyms
Gaboxadol
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (1)
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Journal Impact Factor
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Most Recent
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Can J Physiol Pharmacol
2020 Oct;98(10):725-732. PMID: 32516556
용액&용해도
In Vitro:
DMSO : 50 mg/mL (356.79 mM; ultrasonic and adjust pH to 3 with HCl; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : 23.33 mg/mL (166.48 mM; Need ultrasonic)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (17.84 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (14.84 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: PBS
Solubility: 50 mg/mL (356.79 mM); Clear solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
순도&문서
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Data Sheet (294 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
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]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O / DMSO | 1 mM | 7.1357 mL | 35.6786 mL | 71.3572 mL | 178.3930 mL |
| 5 mM | 1.4271 mL | 7.1357 mL | 14.2714 mL | 35.6786 mL | |
| 10 mM | 0.7136 mL | 3.5679 mL | 7.1357 mL | 17.8393 mL | |
| 15 mM | 0.4757 mL | 2.3786 mL | 4.7571 mL | 11.8929 mL | |
| 20 mM | 0.3568 mL | 1.7839 mL | 3.5679 mL | 8.9197 mL | |
| 25 mM | 0.2854 mL | 1.4271 mL | 2.8543 mL | 7.1357 mL | |
| 30 mM | 0.2379 mL | 1.1893 mL | 2.3786 mL | 5.9464 mL | |
| 40 mM | 0.1784 mL | 0.8920 mL | 1.7839 mL | 4.4598 mL | |
| 50 mM | 0.1427 mL | 0.7136 mL | 1.4271 mL | 3.5679 mL | |
| 60 mM | 0.1189 mL | 0.5946 mL | 1.1893 mL | 2.9732 mL | |
| 80 mM | 0.0892 mL | 0.4460 mL | 0.8920 mL | 2.2299 mL | |
| 100 mM | 0.0714 mL | 0.3568 mL | 0.7136 mL | 1.7839 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
THIP Related Classifications
HY-10232 Related Classifications
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