Description
Vanoxerine dihydrochloride (GBR-12909 dihydrochloride) 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
Vanoxerine dihydrochloride is a Dopamine reuptake inhibitor that is developed for treatment of Parkinson's disease and depression but has no effect on these diseases.
Definition
ChEBI: Vanoxerine dihydrochloride is a hydrochloride salt that is obtained by reaction of vanoxerine with two equivalents of hydrogen chloride. Potent, competitive inhibitor of dopamine uptake (Ki = 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 (IC50 = 48 nM). Centrally active following systemic administration. It has a role as a dopamine uptake inhibitor. It contains a vanoxerine(2+).
General Description
Vanoxerine dihydrochloride is a potent inhibitor of dopamine active transporter (DAT, Ki = 1 nM, IC50 = 40 and 51 nM) with >100 fold selectivity over noradrenalin and 5-HT re-uptake transporter. Shown to produce behavioral profile in mice for bipolar mania disease model and ADHD disease models.
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.
storage
Room temperature (desiccate)
Background
GBR-12909 Dihydrochloride is a highly selective synaptosomal dopamine uptake inhibitor, with a 100-fold stronger affinity for the dopamine uptake carrier protein than noradrenaline and serotonin. GBR-12909 Dihydrochloride has also been demonstrated to be a strong sigma receptor ligand in rat brain samples with an IC50 value of 48 nM. This small molecule is considered to be a high-affinity, long-acting dopamine transporter inhibitor and in vivo models show that intravenous injection of GBR-12909 Dihydrochloride blocks dopamine uptake within 5 seconds, matching the temporal effect of cocaine, with longer-acting and less negative behavioral effects. The ability to regulate dopamine uptake makes GBR-12909 Dihydrochloride a compound of interest when studying substance abuse issues like alcohol and cocaine addiction.
References
1) Andersenet al. (1989),The dopamine inhibitor GBR 12909: selectivity and molecular mechanism of action; Eur. J. Pharmacol.,166493
2) Contreraset al. (1990),GBR-12909 and fluspirilene potently inhibited binding of [3H] (+)3-PPP to sigma receptors in rat brain; Life Sci.,47PL133
3) Yorgasonet al. (2011),Low and high affinity dopamine transporter inhibitors block dopamine uptake within 5 sec of intravenous injection; Neuroscience,182125
