[CAS NO. 67469-81-2] GBR12935dihydrochloride
PRODUCTS SPECIFICATIONS [67469-81-2]
DESCRIPTION [67469-81-2]
Overview
| MDL | MFCD00083175 |
|---|---|
| Molecular Weight | 487.50 |
| Molecular Formula | C28H36Cl2N2O |
| SMILES | N1(CCOC(C2=CC=CC=C2)C3=CC=CC=C3)CCN(CCCC4=CC=CC=C4)CC1.Cl.Cl |
Summary
GBR 12935 dihydrochloride is a potent, and selective dopamine reuptake inhibitor, with the binding constant (K d ) of 1.08 nM in COS-7 cells. GBR 12935 dihydrochloride stimulates the locomotion activity in different mice strains but fails to induce stereotypy. Thus, GBR 12935 dihydrochloride also prevents the d-Fenfluramine-induced head-twitch response in mice [1] [2] [3] [4] .
In Vitro
GBR 12909 (10-100 nM) also shows a high affinity for CYP2D6 with the K
d
value of 42.2 nM, lower than the affinity for dopamine transporter. The binding effect can be reduced by
Quinidine
(HY-B1751) and
Quinine
(HY-D0143), which are the specific and potent inhibitors of CYPZD enzymatic activities
[1]
.
GBR 12935 dihydrochloride (10 nM; 2 min) increases the extracellular levels of dopamine to approximately 400% of basal during the application in the nucleus accumbens
[2]
.
GBR 12935 dihydrochloride (100 μM; 60 min) increases extracellular levels of dopamine compared with levels for artificial cerebrospinal fluid (ACSF) by local perfusion for 60 min
[2]
.
GBR 12935 dihydrochloride (1-9 nM) dose-dependently inhibits active uptake of [
3
H]dopamine in homogenates of the nucleus accumbens
[2]
.
Co-perfusion of 100 μM GBR 12935 dihydrochloride with either 100 μM
Sulpiride
(HY-B1019) or
Raclopride
(HY-103414) produces a significant reduction in the GBR 12935 dihydrochloride induced increase in the extracellular levels of dopamine to basal levels
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GBR 12935 dihydrochloride (1-32 mg/kg; repeat injection; 7 d) elevates locomotion activity to a greater extent in C57BL/6J mice than DBA/2J mice, and (10 mg/kg; injection; 7 d) results few mice sensitized to cocaine-induced stereotypy with repeated injections
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Adult male DBA/2J and C57BL/6J mice (22-30 g) [3] |
| Dosage: | 1.0, 3.2, 10, 32 mg/kg |
| Administration: | Repeat injection; for 7 days |
| Result: |
Elevated locomotion activity to a greater extent in C57BL/6J mice than DBA/2J mice.
No stereotypy was induced by an eighth day challenge of 10 mg/kg GBR 12935 dihydrochloride in mice pretreated with seven dally injections of either 32 mg/kg cocaine or saline. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 25 mg/mL ( 51.28 mM ; Need ultrasonic)
H 2 O : 7.14 mg/mL ( 14.65 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.0513 mL | 10.2564 mL | 20.5128 mL |
| 5 mM | 0.4103 mL | 2.0513 mL | 4.1026 mL |
| 10 mM | 0.2051 mL | 1.0256 mL | 2.0513 mL |
References
- [1] Hiroi T, et al. Specific binding of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl propyl) piperazine (GBR-12935), an inhibitor of the dopamine transporter, to human CYP2D6. Biochem Pharmacol. 1997 Jun 15;53(12):1937-9.
- [2] Rahman S, et al. Negative interaction of dopamine D2 receptor antagonists and GBR 12909 and GBR 12935 dopamine uptake inhibitors in the nucleus accumbens. Eur J Pharmacol. 2001 Feb 23;414(1):37-44.
- [3] Tolliver BK, et al. Comparison of cocaine and GBR 12935: effects on locomotor activity and stereotypy in two inbred mouse strains. Pharmacol Biochem Behav. 1994 Jul;48(3):733-9.
Synonyms