67469-78-7 Usage
Uses
Used in Pharmaceutical Industry:
Vanoxerine dihydrochloride is used as an antidepressant for its ability to effectively inhibit dopamine uptake, leading to the stimulation of dopamine receptors and potentially providing relief from depressive symptoms.
Used in Neurotransmitter Research:
Vanoxerine dihydrochloride is used as a dopamine reuptake inhibitor in the study of dopamine-related neurological processes and disorders. Its high specificity for dopamine makes it a valuable tool for investigating the role of dopamine in various conditions.
Used in Drug Development:
Vanoxerine dihydrochloride is used as a lead compound in the development of new medications targeting dopamine-related conditions. Its potent inhibition of dopamine uptake and interactions with other receptors make it a promising candidate for further research and potential therapeutic applications.
Used in Receptor Binding Studies:
Vanoxerine dihydrochloride is used as a research tool to study the binding properties of various receptors, including histamine H1 receptors and sigma receptors. Its ability to inhibit ligand binding to these receptors can provide insights into receptor function and potential drug interactions.
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 academic research and scientific papers
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.
Aryl 1,4-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake
Van Der Zee,Koger,Gootjes,Hespe
, p. 363 - 370 (2007/10/02)
Substituted 1-[2-(diphenylmethoxy)ethyl]piperazines were synthesized and tested for inhibitory activity on dopamine uptake by synaptosomal preparations of rat corpus striatum. Especially 4-(3-phenyl-2-propenyl)substitution yielded very potent inhibitors with IC50 values of about 1 to 2 nM, activities that surpass that of benztropine 100 times. Compared with other monoamine uptake processes, the effect on dopamine uptake was highly specific. QSAR-analysis showed that substituents in the diphenylmethoxy group combining a strong inductive effect with a small volume provided optimal potency. In contrast, for those in the solitary phenyl group a combination of strong electron-withdrawing effect and a small volume was required.
