67469-78-7 Usage
Description
GBR 12909 is a potent inhibitor that blocks dopamine uptake (IC50 = 1-51 nM). It is more than 100-fold less effective at blocking serotonin or noradrenaline uptake. GBR 12909 effectively inhibits dopamine uptake in vivo, leading to consequent stimulation of dopamine receptors. GBR 12909 also inhibits pyrilamine binding to the histamine H1 receptor (IC50 = 18 nM) but poorly inhibits ligand binding to dopamine, adrenergic, acetylcholine, serotonin, and γ-aminobutyric acid receptors. It also blocks ligand binding to sigma receptors in rat brain (IC50 = 48 nM).
Uses
Different sources of media describe the Uses of 67469-78-7 differently. You can refer to the following data:
1. Antidepressant;Dopamine reuptake inhibitor
2. Dopamine uptake inhibitor
Hazard
A poison.
Biological Activity
Potent, competitive inhibitor of dopamine uptake (K i = 1 nM for inhibition of striatal dopamine uptake). Has > 100-fold lower affinity for the noradrenalin and 5-HT uptake carriers. Also a potent sigma ligand (IC 50 = 48 nM). Centrally active following systemic administration.
Biochem/physiol Actions
Highly selective dopamine reuptake inhibitor with behavioral effects similar to cocaine.
References
1) Andersen?et al. (1989),?The dopamine inhibitor GBR 12909: selectivity and molecular mechanism of action; Eur. J. Pharmacol.,?166?493
2) Contreras?et al. (1990),?GBR-12909 and fluspirilene potently inhibited binding of [3H] (+)3-PPP to sigma receptors in rat brain; Life Sci.,?47?PL133
3) Yorgason?et al. (2011),?Low and high affinity dopamine transporter inhibitors block dopamine uptake within 5 sec of intravenous injection; Neuroscience,?182?125
Check Digit Verification of cas no
The CAS Registry Mumber 67469-78-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,7,4,6 and 9 respectively; the second part has 2 digits, 7 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 67469-78:
(7*6)+(6*7)+(5*4)+(4*6)+(3*9)+(2*7)+(1*8)=177
177 % 10 = 7
So 67469-78-7 is a valid CAS Registry Number.
InChI:InChI=1/C28H32F2N2O.2ClH/c29-26-12-8-24(9-13-26)28(25-10-14-27(30)15-11-25)33-22-21-32-19-17-31(18-20-32)16-4-7-23-5-2-1-3-6-23;;/h1-3,5-6,8-15,28H,4,7,16-22H2;2*1H
67469-78-7Relevant articles and documents
Scale-up synthesis of the dopamine uptake inhibitor GBR-12909
Ironside, Michael D.,Sugathapala, Priyantha M.,Robertson, Jerod,Darey, Mark C.P.,Zhang, Jianzhong
, p. 621 - 627 (2013/09/06)
1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR-12909) is a dopamine uptake inhibitor. The development of a robust process for the preparation of this compound in kilogram quantities is described. The primary aims of the development work were to eliminate chromatographic purifications, to minimize the use of environmentally unacceptable reagents, and to improve the overall yield of the three-step convergent process. These objectives were met, with significant improvements obtained in the key coupling reaction of N-(3-phenylpropyl)piperazine dihydrochloride salt with 1-[bis(4-fluorophenyl)methoxy]-2-chloroethane, which was previously low-yielding and lacking in reproducibility.
