GBR 12783, a potent and selective inhibitor of dopamine uptake: biochemical studies in vivo and ex vivo

European Journal of Pharmacology
J J Bonnet, J Costentin

Abstract

The effects of GBR 12783, an aryl 1,4-dialk(en)ylpiperazine derivative, were studied on the in vivo and ex vivo neuronal uptake of dopamine (DA), norepinephrine (NE) and serotonin (5HT). The drug inhibited potently (IC50 = 1.8 nM) and competitively the [3H]DA uptake by rat striatal synaptosomes. It produced significant [14C]DA release only at much higher concentrations (in the micromolar range). Depending on the animal species (rat or mouse) and the experimental conditions, GBR 12783 was 18-90 times and 85-300 times less effective against NE and 5HT uptake respectively than against DA uptake. In synaptosomes preloaded with [3H]DA, GBR 12783 added to the superfusion medium prevented the (+)amphetamine-induced DA release. The total binding of [3H]GBR 12783 to a membranal fraction prepared from striatum was lower than the binding to a synaptosomal fraction, suggesting its entry in synaptosomes. In addition, the concentration-dependent release of [3H]DA produced by GBR 12783 from a striatal vesicular fraction may account for the synaptosomal DA release promoted by micromolar concentrations of the drug. In ex vivo experiments, the ID50 for DA uptake inhibition (30 min after i.p. administration) was 8.1 mg/kg. After a dose of 10 mg/k...Continue Reading

References

Jan 1, 1977·British Journal of Clinical Pharmacology·U SchachtG Bäcker
Jul 26, 1973·Naunyn-Schmiedeberg's Archives of Pharmacology·A Philippu, J Beyer
Jan 29, 1981·European Journal of Pharmacology·L E Dyck
Aug 17, 1984·European Journal of Pharmacology·R E Heikkila, L Manzino
Oct 1, 1984·Biochemical Pharmacology·W J KinnierL Y Norrell

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Citations

Jan 1, 1990·Journal of Neural Transmission. General Section·B NaudinJ Costentin
Jan 1, 1992·Journal of Neural Transmission. General Section·F MennickenC Feuerstein
Jan 1, 1994·Journal of Neural Transmission. General Section·E ChanutC Jacquot
Jul 18, 1989·European Journal of Pharmacology·Y L Hurd, U Ungerstedt
Aug 3, 1989·European Journal of Pharmacology·P H Andersen
Jan 7, 1992·European Journal of Pharmacology·J M VaugeoisJ Costentin
Feb 21, 1994·European Journal of Pharmacology·M E ReithN H Chen
Jul 1, 1993·Pharmacology, Biochemistry, and Behavior·P SimonJ Costentin
Aug 1, 1994·Pharmacology, Biochemistry, and Behavior·C S Maldonado-IrizarryA E Kelley
May 1, 1994·Pharmacology, Biochemistry, and Behavior·G A van der Hoek, S J Cooper
May 1, 1996·Pharmacology, Biochemistry, and Behavior·J M VaugeoisJ Costentin
Jun 19, 1992·Brain Research. Developmental Brain Research·W D LeS H Appel
Mar 31, 1994·Behavioural Brain Research·P SimonJ Costentin
Jan 1, 1990·Progress in Neurobiology·A S Horn
Jul 1, 1991·Brain Research Bulletin·B A Baldo, A E Kelley
Nov 15, 1993·European Journal of Pharmacology·G BillaudJ J Bonnet
Mar 29, 2001·Pharmacology, Biochemistry, and Behavior·M TrzcińskaJ W Babich
Feb 3, 1999·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·J Garcia de Mateos-VerchereJ Costentin
Sep 18, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Emmanuel ValjentJean-Antoine Girault

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