Disease relevance of Vanoxerine

• However, GBR-12909 significantly decreased the severity of those duodenal ulcers that were produced [1].
• Treatment with the specific DA transport blocker GBR 12909 during anoxia resulted in a significant increase in DA to 236% over basal levels [2].
• Interestingly, GBR 12909 protects CGNs from both MPP+ and rotenone toxicity [3].
• A major effect of BSO alone or in combination with GBR 12909 was the induction of cataracts in both sexes, whereas GBR 12909 induced an elevation of body weight in females only [4].

Psychiatry related information on Vanoxerine

• RESULTS: Amphetamine and methylphenidate decreased impulsive decision making, which was mimicked by the selective dopamine reuptake inhibitor GBR 12909 but not by the noradrenaline reuptake inhibitor desipramine [5].
• Following GBR-12909 administration, all subjects showed dose dependent increases in sniffing, locomotor activity, and rearing [6].
• BSO and GBR 12909 alone or in combination minimally affected the development of spontaneous alternation or basic sensory and motor skills [4].
• Individual differences in behavior following amphetamine, GBR-12909, or apomorphine but not SKF-38393 or quinpirole [6].
• Between these days, the paired Chronic-before group was injected (every other day) with GBR 12909 prior to intracranial self-stimulation, while unpaired, Chronic-after group was given the drug just after the end of the session [7].

High impact information on Vanoxerine

• DAT-siRNA infusion in adult mice produced a significant down-regulation of DAT mRNA and protein in the brain and also elicited a temporal hyperlocomotor response similar to that (but delayed) obtained upon infusion of GBR-12909, a pharmacologically selective DAT inhibitor [8].
• Thus, amphetamine, GBR-12909, apomorphine, and the combined administration of D1 and D2 agonists all facilitate ascorbate release from glutamatergic terminals in the neostriatum, and this effect is blocked by dopamine receptor antagonists [9].
• By contrast, TTX greatly attenuated the Fos response evoked by cocaine or GBR 12909 [10].
• L-Dopa or GBR-12909 improved upper limb motor performance by up to 40% in the aged animals [11].
• Nevertheless, substitution of GBR-12909 for cocaine reversed the cocaine-induced upregulation of DA transporters and reduced DA and dihydroxyphenylacetic acid levels in the mesolimbic system [12].

Chemical compound and disease context of Vanoxerine

• Cocaine, GBR 12909, and BZT analogs each displaced [125I]RTI-121 and stimulated locomotor activity in a dose- and time-dependent manner [13].
• Selective DA transport inhibitors GBR-12909 and amfonelic acid greatly stimulated motor activity in sham control subjects, too, but did not antagonize hyperactivity in lesioned rats [14].
• The levels of dopamine and its metabolites were examined 40 min after the administration of GBR 12909 and/or apomorphine, when the effects of the drugs on locomotor activity were approximately at a peak [15].
• In contrast to its effect on learning, SCH 23390 (0.025 and 0.05 mg/kg) was more effective to suppress the stimulant effect of GBR 12909 on locomotor activity than was (-)-sulpiride (40 and 80 mg/kg) [16].
• We also report that compounds (pargyline and GBR-12909) which block MPTP's toxicity in vivo and prevent non-reversible changes in synaptic transmission are not able to alter MPTP's ability to decrease slice dopamine contents [17].

Biological context of Vanoxerine

• One of the enantiomers, compound S,S-(-)-19a, exhibited the highest potency for the DAT (IC50 = 11.3 nM) among all the compounds tested and was as potent as GBR 12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine) [18].
• MDMA administration increased lipid peroxidation in striatal synaptosomes, an effect reduced by approximately 60% by GBR 12909 pre-treatment [19].
• A comprehensive hierarchical clustering study of two GBR 12909 analogs was performed to identify representative conformers for input to three-dimensional quantitative structure-activity relationship studies of closely-related analogs [20].
• GBR 12909 (0.5-10 mg/kg) elicited a decrease in cardiac output at higher doses [21].
• An increase in the number of [3H]mazindol binding sites in the striatum was seen with L-DOPA and GBR 12909 [22].

Anatomical context of Vanoxerine

• The extracellular level of dopamine in the nucleus accumbens was also increased by perfusion of a selective dopamine re-uptake inhibitor 1-[2-[bis(4-fluorophenyl)methoxy]-4-(3-phenylpropyl)piperazine (GBR-12909) in the nucleus accumbens [23].
• Furthermore, [3H]dopamine accumulation was prevented by coincubation of oocytes with dopamine (100 microM) or with the dopamine uptake inhibitors GBR 12909 (1 microM) or cocaine (3 microM) [24].
• The GBR 12909 effects on adrenal DA and heart Ad were blocked by raclopride, but not by domperidone, suggesting a central site of action. d-Amphetamine, in both doses used (2.5 and 5 mg/kg) induced a statistically significant decrease in forebrain DOPAC between 30 min and 2 hr, and an increase in adrenal DA [25].
• GBR 12909 elevated 3MT production only in the hypothalamus, the striatum and the nucleus accumbens [26].
• In the NA-rich prefrontal cortex only DMI increased extracellular DA concentrations whereas in the dorsal caudate only GBR 12909 was effective [27].

Associations of Vanoxerine with other chemical compounds

• Unlike cocaine, GBR-12909 self-administration by itself altered neither DA transporters nor D1 or D2 receptors [12].
• In vivo microdialysis and thermospray tandem mass spectrometry of the dopamine uptake blocker 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)-piper azine (GBR-12909) [28].
• The D1 antagonist SCH-23390 blocked GBR-12909-induced activation of Fos while potentiating the stimulation of DA output [29].
• Studies, using in vivo microdialysis, on the effect of the dopamine uptake inhibitor GBR 12909 on 3,4-methylenedioxymethamphetamine ('ecstasy')-induced dopamine release and free radical formation in the mouse striatum [19].
• The relative efficacy of the compounds (BTS 74 398 > GBR 12909 > nomifensine >> bupropion) paralleled their potency in inhibiting DA uptake in vitro and in vivo [30].

Gene context of Vanoxerine

• When pregnant mice from +¿- x +¿- matings were injected with the D1 receptor agonist SKF 38393, or the dopamine reuptake blocker GBR 12909 at day 19 of gestation, c-fos mRNA expression was observed in the SCN of +/+ fetuses [31].
• In addition, GBR-12909 partially attenuated MPP+ (40 nmol)-caused a loss of striatal nerve terminal as indicated by decreases in TH and DAT immunoreactivities as well as dopamine and its metabolites levels [32].
• Unexpectedly, hyperactivity induced by 20 mg/kg GBR 12909 was attenuated only in male COMT knockout mice, i.e., they had an inability to sustain the hyperactivity induced by DAT inhibition [33].
• Further, when COMT knockout mice were challenged with l-dopa or a dopamine transporter (DAT) inhibitor, an accumulation of dopamine occurred and the neurochemical and locomotor effects of l-dopa and GBR 12909 were modified accordingly [34].
• DAT-siRNA infusion in adult mice produced a significant down-regulation of DAT mRNA and protein and elicited hyperlocomotion similar, but delayed, to that produced on infusion of GBR-12909, a potent and selective DAT inhibitor [35].

Analytical, diagnostic and therapeutic context of Vanoxerine

• Microdialysis in conjunction with thermospray tandem mass spectrometry was employed in following the time course of the experimental drug GBR-12909 in vivo [28].
• Activation of the feedback system was accomplished by perfusion of the ACB with the DA uptake inhibitor GBR 12909 (GBR; 100 microm) [36].
• Amphetamine-evoked dopamine release and release after injection of the selective dopamine reuptake blocker GBR 12909 were attenuated after a near-complete denervation of the SN (5 weeks after lesioning) [37].
• Extracellular dopamine (DA) concentrations estimated by transcerebral dialysis and D1-dependent c-fos expression, as demonstrated by Fos immunohistochemistry, were studied after blockade of DA reuptake by GBR-12909 [29].
• CONCLUSIONS: These data suggest a preferred profile of effects of GBR 12909 as an anti-cocaine pharmacotherapy [38].

References