[3H]WIN 35,065–2: A Ligand for Cocaine Receptors in Striatum

  title={[3H]WIN 35,065–2: A Ligand for Cocaine Receptors in Striatum},
  author={Mary C. Ritz and John W. Boja and Dimitri E. Grigoriadis and Robert C. Zaczek and F. Ivy Carroll and Amanda H Lewis and Michael J. Kuhar},
  journal={Journal of Neurochemistry},
Abstract: [3H]WIN 35,065–2 binding to striatal membranes was characterized, primarily by centrifugation assay. Like [3H]cocaine, [3H]WIN 35,065–2 binds to both high‐ and low‐affinity sites. [3H]WIN 35,065–2, however, exhibits consistently higher affinities than [3H]cocaine. Saturation experiments indicate a low‐affinity binding site with an apparent KD of ∼ 160 nM and a Bmaxof 135 fmol/mg of tissue. A high‐affinity site has also been identified with an apparent KD of 5.6 nM and a Bmax of 5.2… 

[125I]RTI‐55 Binding to Cocaine‐Sensitive Dopaminergic and Serotonergic Uptake Sites in the Human Brain

It appears that [125I]RTI‐55 should be useful in further studies of the regulation of cocaine binding sites using postmortem human specimens, and may offer advantages over other ligands previously used to examine cocainebinding sites.

Heterogeneous subregional binding patterns of 3H-WIN 35,428 and 3H-GBR 12,935 are differentially regulated by chronic cocaine self- administration

  • J.M.M. WilsonJN Nobrega S. Kish
  • Biology, Psychology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1994
The data suggest that dopamine transporter concentration, and perhaps function, might undergo up- or downregulation, either as a direct effect of cocaine, or indirectly as part of a homeostatic response to altered synaptic dopamine levels, and therefore might participate in the neuronal events underlying cocaine-induced behavioral changes.

Studies of the biogenic amine transporters. 1. Dopamine reuptake blockers inhibit [3H]mazindol binding to the dopamine transporter by a competitive mechanism: Preliminary evidence for different binding domains

Although the ligand-selectivity of the [3H]mazindol binding site indicates that it is the uptake inhibitor recognition site of the classic DA transporter, the quantitative differences among the ligands-selectivities of different radioligands for the same site suggest that each radiolIGand labels different overlapping domains of the DA uptake inhibitors recognition site.

High Potency Cocaine Analogs: Neurochemical, Imaging, and Behavioral Studies

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.

Pharmacological effects of dopaminergic drugs on in vivo binding of [99mTc]TRODAT-1 to the central dopamine transporters in rats

The results suggest that prior knowledge of whether patients are receiving various drug treatments may assist in the interpretation of DAT status as assessed by SPET imaging studies using [99mTc]TRODAT-1.

In vitro characterization of cocaine binding sites in human hair.

Multivariate analysis indicated that significantly greater nonspecific and specific radioligand binding occurred in dark hair than in light hair, and a significant ethnicity x sex effect on specific and nonspecial binding to hair.

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

There was no obvious correlation between rate of occupancy in this animal model and abuse liability in humans, which is consistent with the notion that other factors are critical as well.

In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [11C]WIN 35,428

In studies with a baboon, [11C]WIN 35,428 accumulated in brain regions containing dopamine transporters, i.e., the striata, and imaging of D2 dopamine receptors with [ 11C]NMSP in the same MPTP‐treated animals showed much less reduction in the postsynaptic D1 dopamine receptors.

Rat mesencephalic neuronal cells cultured for different periods as a model of dopamine transporter ontogenesis

The development of high-affinity [3H]WIN 35,428 binding sites in neurons cultured for different time periods could be a useful model of dopamine transporter ontogenesis.



High affinity stereospecific binding of [3H] cocaine in striatum and its relationship to the dopamine transporter.

It is suggested that the cocaine receptor in the striatum may be an allosteric protein with mazindol and cocaine binding to overlapping sites, while Na+ and DA are allosterics modulators, which stabilize a lower affinity state for cocaine.

Central and peripheral cocaine receptors.

Binding of cocaine to both brain and liver membranes was sensitive to proteases, reduced by high Na+ concentrations (30-100 mM), eliminated by denaturing temperatures (i.e., 95 degrees C for 5 min) and optimal at pH 7.4.

Effects of cocaine and related drugs in nonhuman primates. I. [3H]cocaine binding sites in caudate-putamen.

Binding of [3H]cocaine was NaCl-dependent, with specific binding reduced by 72% when NaCl (100 mM) was omitted from the incubation medium, and dopamine was considerably more potent than either norepinephrine or serotonin.

Cocaine receptors labeled by [3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane.

The results show that [ 3H]CFT and [3H]cocaine bind to a similar spectrum of sites in monkey caudate putamen, with a high positive correlation (r, 0.99, p less than 0.001) between the affinities of drugs at sites labeled by [3h]C FT and [4-fluorophenyl)-tropane.

Biochemical and Pharmacological Characterization of [3H]GBR 12935 Binding In Vitro to Rat Striatal Membranes: Labeling of the Dopamine Uptake Complex

DA uptake and the DA uptake binding site of [3H]GBR 12935 were located primarily in the striatum, but the piperazine acceptor site was distributed uniformly throughout the brain, and inhibitors of DA uptake label the carrier site and prevent the carrier process.

Characterization of Sodium‐Dependent [3H]GBR‐12935 Binding in Brain: A Radioligand for Selective Labelling of the Dopamine Transport Complex

Data indicate that [3H]GBR‐12935 is a selective radioligand of the presynaptic dopamine transport complex in brain, with the highest concentration of binding sites being found in the corpus striatum and nucleus accumbens.

Similarities and Differences Between High‐Affinity Binding Sites for Cocaine and Imipramine in Mouse Cerebral Cortex

The data suggest that the high‐affinity binding sites for [3H]cocaine and [ 3H]imipramine in the cerebral cortex are distinct entities.