GBR 12935 dihydrochloride

Names

[ Name ]:
GBR 12935 dihydrochloride

[Synonym ]:
1-[2-(benzhydryloxy)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride
1-[2-(Diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride
Piperazine, 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-, hydrochloride (1:2)
1-(2-DIPHENYLMETHOXYETHYL)-4-(3-PHENYLPROPYL)PIPERAZINE DIHYDROCHLORIDE
GBR 12935 dihydrochloride
GBR 12935 (dihydrochloride)

Biological Activity

[Description]:

GBR 12935 2Hcl is a potent, and selective dopamine reuptake inhibitor.IC50 value: Target: dopamine reuptake inhibitorin vitro: The calculated Kd of [3H]GBR-12935 binding to CYP2D6 was 42.2 nM, indicating that GBR-12935 has a high affinity for CYP2D6. The binding of [3H]GBR-12935 to CYP2D6 was decreased partially by substrates or inhibitors of CYP2D isoforms (quinine, quinidine, propranolol, bufuralol, imipramine, and desipramine) [1]. Co-perfusion of 100 microM GBR 12909 or GBR 12935 with either 100 microM sulpiride or raclopride produced a significant reduction in the GBR 12909 or GBR 12935 induced increase in the extracellular levels of dopamine to basal levels. In vitro, GBR 12909 (1-9 nM) dose-dependently inhibited active uptake of [3H]dopamine in homogenates of the nucleus accumbens [2].in vivo: GBR 12935 elevated locomotion to a greater extent in C57BL/6J mice at the maximally active dose of 10 mg/kg. Locomotor stimulation by GBR 12935 remained consistent in both strains with repeated injections. DBA/2J mice became sensitized to cocaine-induced stereotypy with repeated injections. Cocaine induced no stereotypy in C57BL/6J mice on any test day. No stereotypies were induced by GBR 12935 in either strain on any test day [3].

[Related Catalog]:

Signaling Pathways >> Neuronal Signaling >> Dopamine Transporter

Research Areas >> Neurological Disease

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
564ºC at 760 mmHg

[ Molecular Formula ]:
C₂₈H₃₆Cl₂N₂O

[ Molecular Weight ]:
487.504

[ Flash Point ]:
294.9ºC

[ Exact Mass ]:
486.220459

[ PSA ]:
15.71000

[ LogP ]:
6.52280

[ Appearance of Characters ]:
white solid

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Articles

Plasma membrane monoamine transporters: structure, regulation and function.

Nat. Rev. Neurosci. 4 , 13-25, (2003)

Studies of the biogenic amine transporters. III. Demonstration of two binding sites for [3H]GBR12935 and [3H]BTCP in rat caudate membranes.

J. Pharmacol. Exp. Ther. 268 , 1462-1475, (1994)

The present study addressed the hypothesis that there exist multiple sites/states associated with the dopamine (DA) transporter ligands. The authors used [3H](1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylp...

[3H]GBR-12935 binding to cytochrome P450 in the human brain.

J. Neurochem. 62 , 342-348, (1994)

The presence of multiple [3H]GBR-12935 binding sites in the human brain has been revealed in several recent studies. One site represents the dopamine uptake site. In rat brain it was demonstrated that...