| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary target of GBR 12935 is the dopamine transporter (DAT), where it potently binds to inhibit dopamine reuptake. This compound exhibits high selectivity for DAT: in rat striatal membranes, it has a Ki of 3.7 nM for DAT; in COS-7 cells, it has a Kd of 1.08 nM. The binding affinity for the norepinephrine transporter (NET) is Ki = 630 nM, and for the serotonin transporter (SERT) Ki = 2,090 nM, demonstrating >500-fold selectivity for DAT. Additionally, GBR 12935 has moderate affinity for sigma non-opioid intracellular receptor 1 (IC₅₀ = 17 nM) and exhibits specific binding to human CYP2D6.
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|---|---|
| ln Vitro |
In vitro studies demonstrate that GBR 12935 functions by inhibiting DAT-mediated dopamine reuptake. In the nucleus accumbens, 10 nM GBR 12935 elevates extracellular dopamine levels to approximately 400% of basal values within 2 minutes of application. This compound dose-dependently inhibits [³H]-dopamine uptake in rat striatal homogenates, with a pIC₅₀ of 7.74 at the human DAT (IC₅₀ ≈ 18 nM). In nucleus accumbens homogenates, 1-9 nM GBR 12935 dose-dependently inhibits active [³H]dopamine uptake. Furthermore, GBR 12935 also inhibits dopamine uptake into brain synaptic vesicles (concentrations of 34-45 nM required, one order of magnitude higher than for neuronal uptake inhibition).
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| ln Vivo |
In vivo studies demonstrate that GBR 12935 dose-dependently increases locomotor activity in mice. In C57BL/6J and DBA/2J inbred mouse strains, intraperitoneal administration of GBR 12935 (10 mg/kg) significantly enhances locomotor activity compared to vehicle, but does not induce stereotypy at any tested dose. Unlike cocaine, GBR 12935 does not induce sensitization to stereotypy following repeated injections. Additionally, injection of GBR 12935 into the rostral agranular insular cortex of rats produces dose-dependent antinociception and prevents the d-fenfluramine-induced head-twitch response in mice. This compound also inhibits GABA-induced chloride influx and antagonizes the effects of muscimol on rat cerebellar Purkinje cells.
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| Enzyme Assay |
DAT Competition Binding Assay: Prepare rat striatal membranes, incubate with varying concentrations of GBR 12935 (0.01-100 μM) and [¹²⁵I]-RTI-55, detect radioactivity by filtration and liquid scintillation counting, and calculate a Ki of 3.7 nM for DAT.
Sigma Receptor Binding Assay: Use [³H]-(+)-pentazocine as radioligand and frozen guinea pig brain membranes as receptor source, incubate with varying concentrations of the compound, and determine an IC₅₀ of 17 nM for the σ1 receptor.
CYP2D6 Binding Assay: Incubate human liver microsomes enriched in CYP2D6 with [³H]-GBR 12935, separate by ultracentrifugation, and detect bound radioactivity.
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| Cell Assay |
Dopamine Uptake Inhibition Assay (Synaptosomes): Dissect rat striatum and homogenize in ice-cold buffer, centrifuge to obtain crude synaptosomal fraction. Incubate synaptosomes with varying concentrations of GBR 12935 and [³H]-dopamine for 15 minutes at 37°C, filter and detect radioactivity to determine uptake inhibition.
Dopamine Uptake Inhibition Assay (Cell Lines): Use HEK293 cells expressing the human dopamine transporter, incubate with varying concentrations of the compound and [³H]-dopamine, and determine an IC₅₀ of 18 nM.
Synaptic Vesicle Uptake Assay: Isolate brain synaptic vesicles, incubate with 34-45 nM GBR 12935 and [³H]-dopamine, and detect inhibition of dopamine uptake into vesicles.
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| Animal Protocol |
Animal Models: Use adult male DBA/2J and C57BL/6J mice (22-30 g) for behavioral studies.
Dosing Regimen: Dissolve GBR 12935 fumarate in saline and administer via intraperitoneal injection. Dose range is 1-40 mg/kg. For repeat injection studies, administer daily for 7 days.
Behavioral Assessment: Measure locomotor activity (distance traveled) and stereotypy for 120 minutes using an automated activity monitoring system. In the rat rostral agranular insular cortex injection model, assess antinociception using the formalin test.
Data Analysis: Compare locomotor activity, stereotypy, and dopamine levels between treatment and control groups.
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| References |
|
| Molecular Formula |
C32H38N2O5
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|---|---|
| Molecular Weight |
530.65
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| Exact Mass |
530.2780723
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| Elemental Analysis |
C, 72.43; H, 7.22; N, 5.28; O, 15.07
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| CAS # |
1349767-56-1
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| Related CAS # |
1349767-56-1; 67469-81-2 (2HCl); 76778-22-8
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| Appearance |
Typically exists as solids at room temperature
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| Boiling Point |
540.6°C at 760 mmHg
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| LogP |
0
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| SMILES |
C(/C(=O)O)=C/C(=O)O.C(C1C=CC=CC=1)(C1C=CC=CC=1)OCCN1CCN(CCCC2C=CC=CC=2)CC1
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| Chemical Name |
1-(2-benzhydryloxyethyl)-4-(3-phenylpropyl)piperazine;(Z)-but-2-enedioic acid
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| Synonyms |
GBR12935 fumarate; GBR-12935 fumarate; GBR 12935 fumarate; GBR-12935 maleate; GBR 12935 Dimaleate Salt; 1349767-56-1; GBR 12935 Dimaleate Salt; 1-(2-(Benzhydryloxy)ethyl)-4-(3-phenylpropyl)piperazine maleate; CHEMBL434080; 1-[2-(Diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine Dimaleate Salt;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8845 mL | 9.4224 mL | 18.8448 mL | |
| 5 mM | 0.3769 mL | 1.8845 mL | 3.7690 mL | |
| 10 mM | 0.1884 mL | 0.9422 mL | 1.8845 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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