Rate of binding of various inhibitors at the dopamine transporter in vivo

@article{Stathis2005RateOB,
  title={Rate of binding of various inhibitors at the dopamine transporter in vivo},
  author={Marigo Stathis and Ursula A Scheffel and Susan Z. Lever and John W. Boja and Michael J. Kuhar and F. Ivy Carroll},
  journal={Psychopharmacology},
  year={2005},
  volume={119},
  pages={376-384}
}
The rate of entry of drugs into brain is thought to be a factor in their abuse liability. In this investigation, we have examined the rate of entry and binding at dopamine transporters in mouse striatum for a variety of dopamine transporter inhibitors. The method utilized was based on measuring the displacement of3H-WIN 35,428 from striatal dopamine transporter sites in vivo at different times. Eleven cocaine analogs (RTI-31, RTI-32, RTI-51, RTI-55, RTI-113, RTI-114, RTI-117, RTI-120, RTI-121… 
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References

SHOWING 1-10 OF 88 REFERENCES
Behavioral effects of novel cocaine analogs: a comparison with in vivo receptor binding potency.
TLDR
Results support the hypothesis of a relationship between binding at the dopamine transporter and the behavioral effects of cocaine-like drugs and suggest that maximal locomotor effects occur with near total occupancy of transporter binding sites.
In vivo labeling of cocaine binding sites on dopamine transporters with [3H]WIN 35,428.
TLDR
After in vivo administration, [3H]WIN 35,428 is a suitable ligand for labeling cocaine receptors associated with dopamine transporters in vivo and the in vivo potency of cocaine analogs correlated with their in vitro potency.
Occupancy of the serotonin transporter by fluoxetine, paroxetine, and sertraline: In vivo studies with [125i]rti‐55
TLDR
The results indicate that in competition studies, [125I]RTI‐55 can be used to identify doses of drugs that are physiologically effective, to determine their relative rate of occupancy, and most importantly, to measure the residency time on the central serotonin transporter in vivo.
Cocaine receptors on dopamine transporters are related to self-administration of cocaine.
TLDR
It is shown here that the potencies of cocaine-like drugs in self-administration studies correlate with their potencies in inhibiting [3H]mazindol binding to the dopamine transporters in the rat striatum, but not with theirPotencies in binding to a large number of other presynaptic and postsynaptic binding sites.
Dopamine transporter: biochemistry, pharmacology and imaging.
TLDR
In vivo labeling studies of the dopamine transporter have revealed the usefulness of imaging the transporter, a measure of the presence of dopaminergic nerve terminals, as a potential diagnostic tool in Parkinson's disease.
High Potency Cocaine Analogs: Neurochemical, Imaging, and Behavioral Studies
TLDR
In order to correctly identify the molecular structural requirements fbr cocaine binding one must utilize cocaine or cocaine analogs, which have been radioactively labeled and have proven to be superior ligands in vim binding studies when compared to cocaine.
Mapping cocaine binding sites in human and baboon brain in vivo
TLDR
The feasibility of using [11C]cocaine and PET to map binding sites for cocaine in human brain, to monitor its kinetics, and to characterize its binding mechanism by using appropriate pharmacological challenges is demonstrated.
Pet study of [11C] β‐CIT binding to monoamine transporters in the monkey and human brain
TLDR
The finding indicates that cocaine arousal may be induced at a low dopamine transporter occupancy of a few percent, and β‐CIT should be a useful radioligand to explore cocaine actions in humans and to follow the pathophysiological process in vivo by PET in neurodegenerative diseases of the striatum.
[3H]WIN 35,065–2: A Ligand for Cocaine Receptors in Striatum
TLDR
Pharmacological characterization suggests that [3H]WIN 35,065–2 binds to the dopamine transporter, and the effect of sodium on binding was examined under conditions in which the low‐affinity site was primarily occupied and ∼50% of both sites were occupied, indicating that both sites are sodium dependent.
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