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Tiagabine (NO050328; NO328; TGB) is an orally active, highly selective, and reversible GAT-1 inhibitor and anticonvulsant that crosses the blood-brain barrier. By blocking the reuptake of GABA in neurons and glial cells, tiagabine increases extracellular GABA levels to enhance inhibitory signal transduction, thereby exerting multiple activities such as anticonvulsant, neuroprotective, and antioxidant effects. Tiagabine exhibits linear pharmacokinetic properties. Although it is metabolized by CYP3A and has a high protein binding rate, it carries a low risk of cognitive impairment. Tiagabine is widely used in research on related diseases including epilepsy (including refractory partial seizures), alcohol withdrawal symptoms, and Huntington's disease.
For research use only. We do not sell to patients.
Tiagabine (NO050328; NO328; TGB) is an orally active, highly selective, and reversible GAT-1 inhibitor and anticonvulsant that crosses the blood-brain barrier. By blocking the reuptake of GABA in neurons and glial cells, tiagabine increases extracellular GABA levels to enhance inhibitory signal transduction, thereby exerting multiple activities such as anticonvulsant, neuroprotective, and antioxidant effects. Tiagabine exhibits linear pharmacokinetic properties. Although it is metabolized by CYP3A and has a high protein binding rate, it carries a low risk of cognitive impairment. Tiagabine is widely used in research on related diseases including epilepsy (including refractory partial seizures), alcohol withdrawal symptoms, and Huntington's disease[1][2][3][4][5][6].
Cellular Effect
Cell Line
Type
Value
Description
References
HEK293
IC50
0.07 μM
Compound: 5
Inhibition of [3H]GABA uptake at mouse GAT1 expressed in HEK293 cells after 25 mins by scintillation counting analysis
Inhibition of [3H]GABA uptake at mouse GAT1 expressed in HEK293 cells after 25 mins by scintillation counting analysis
Inhibition of mouse mGAT1 expressed in HEK293 cells assessed as inhibition of [3H]GABA uptake after 3 mins incubation by TopCount microplate scintillation counting analysis
Inhibition of mouse mGAT1 expressed in HEK293 cells assessed as inhibition of [3H]GABA uptake after 3 mins incubation by TopCount microplate scintillation counting analysis
Inhibition of mouse mGAT2 expressed in HEK293 cells assessed as inhibition of [3H]GABA uptake after 3 mins incubation by TopCount microplate scintillation counting analysis
Inhibition of mouse mGAT2 expressed in HEK293 cells assessed as inhibition of [3H]GABA uptake after 3 mins incubation by TopCount microplate scintillation counting analysis
Inhibition of mouse mGAT4 expressed in HEK293 cells assessed as inhibition of [3H]GABA uptake after 3 mins incubation by TopCount microplate scintillation counting analysis
Inhibition of mouse mGAT4 expressed in HEK293 cells assessed as inhibition of [3H]GABA uptake after 3 mins incubation by TopCount microplate scintillation counting analysis
Inhibition of mouse mGAT3 expressed in HEK293 cells assessed as inhibition of [3H]GABA uptake after 3 mins incubation by TopCount microplate scintillation counting analysis
Inhibition of mouse mGAT3 expressed in HEK293 cells assessed as inhibition of [3H]GABA uptake after 3 mins incubation by TopCount microplate scintillation counting analysis
Tiagabine (0.1-5 μM; 4 days) protects Tet-off PC12 cells expressing mutant huntingtin against toxicity, with significant effects detected at concentrations of 0.5, 2, and 5 μM after 4 days of treatment[1]. Tiagabine potently and selectively inhibits GABA uptake in glial, neuronal, and synaptosomal preparations, with IC50 values of 0.18 μmol/L, 0.45 μmol/L, and 0.07 μmol/L, respectively[3]. Tiagabine (2-100 μM; 5-15 min) induces long-lasting, repetitive slow depolarizations in cortical wedges from 20-30 day-old DBA/2 mice, with consistent amplitude and frequency across tested concentrations of 2, 5, 50, and 100 μM following 15-min perfusion, and following shorter 5-10 min perfusions of 50 μM[4]. Tiagabine (50 μM; 15 min)-induced depolarizations in cortical wedges from 20-30 day-old DBA/2 mice are Ca2+-dependent, mediated via GABAA receptors, require voltage-dependent sodium channel activity, are unaffected by NMDA receptor blockade, are partially inhibited by AMPA receptor blockade, are abolished by Dextromethorphan, and are potentiated by potassium channel blockade[4]. Tiagabine (50 μM; 15 min) induces depolarizations in cortical wedges from 50 day-old DBAr2 mice and BALB/c mice, similar to responses in 20-30 day-old DBAr2 mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Inhibited LDH release induced by mutant htt in a concentration-dependent manner. Showed statistically significant reductions in LDH release at 0.5, 2, and 5 μM compared to untreated mutant htt-expressing cells.
Tiagabine (2-5 mg/kg; i.p., daily administration, lifelong treatment) extends the survival of male N171-82Q transgenic Huntington's disease mice (up to 33.4 days at the 5 mg/kg dose), improves their motor function, and alleviates brain atrophy and neurodegeneration[1]. Tiagabine (5 mg/kg; i.p.; daily; lifelong administration) extends the survival of male and female R6/2 transgenic Huntington's disease mice (17.8 days of extension at the dose of 5 mg/kg), improves their motor function, and alleviates brain atrophy[1]. Tiagabine (0.4 mg/kg; i.p.; single administration; 30 min prior to seizure testing) exerts a protective effect against audiogenic tonic seizures in male DBA/2 mice, with an ED50 of 0.4 mg/kg[2]. Tiagabine (1.2-1.3 mg/kg; i.p.; single administration; 30 min prior to seizure tests) exerts a protective effect against PTZ-induced tonic convulsions in male NMRI mice, with an ED50 of 1.2 mg/kg, while providing approximately 50% partial protection against clonic convulsions[2]. Tiagabine (15-30 mg/kg; p.o.; twice daily; for consecutive 21 days) induces tolerance to cognitive effects in mice, but does not induce tolerance to its anticonvulsant effects in DMCM-induced epileptic mice[3]. Tiagabine (9 mg/kg; subcutaneous injection; once daily for 8 consecutive days; single injection 30 min prior to locomotor activity test) initially reduces short-term spontaneous ethanol intake in ad libitum-fed C57BL/6 mice, but tolerance develops rapidly, resulting in ethanol intake exceeding pre-treatment levels on days 7-8[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Increased average survival to 102.0 ± 2.9 days compared to 84.2 ± 3.5 days in vehicle controls. Improved rotarod performance at 10 and 12 weeks of age with statistically significant increases in time on the rod relative to vehicle-treated mice. Increased striatal volume and reduced lateral ventricle volume relative to vehicle-treated mice, attenuating brain atrophy. Showed no effect on the number of huntingtin aggregates in the frontal cortex or striatum, and did not affect body weight loss in HD mice.
Animal Model:
C57BL/6 mice with Alcohol use disorder (male, initially 7 weeks old, food-restricted to 80% of ad libitum body weight)[5]
Dosage:
1 mg/kg; 3 mg/kg; 6 mg/kg; 9 mg/kg
Administration:
s.c.; single injection 30 minutes prior to test; daily for 13 days; single injection 30 minutes prior to post-prandial test
Result:
Produced dose-responsive reductions in lever responses, fountain contacts, and ethanol intake during pre-prandial testing. Significantly reduced all three measures at 6 mg/kg and 9 mg/kg doses compared to saline. Reduced lever responses across 13 days of daily 9 mg/kg administration with no evidence of tolerance. Developed tolerance to the reduction of fountain contacts by the second week of 9 mg/kg daily treatment. Reduced lever responses at 6 mg/kg, and reduced lever responses, fountain contacts, and ethanol intake at 9 mg/kg during post-prandial testing compared to saline. Reduced lever responses for ethanol by 43% at 9 mg/kg, a significantly greater reduction than the 26% reduction observed for water. Reduced motor activity by ~45% on the first day of 9 mg/kg administration, but tolerance to this sedative effect developed by the third daily injection.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (266.28 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.6628 mL
13.3138 mL
26.6276 mL
5 mM
0.5326 mL
2.6628 mL
5.3255 mL
10 mM
0.2663 mL
1.3314 mL
2.6628 mL
View the 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.
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.
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO 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.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.66 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 μLDMSO stock solution (25.0 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.
Protocol 3
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.66 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
*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.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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