In Vivo Characterization of a Novel Phenylisothiocyanate Tropane Analog at Monoamine Transporters in Rat Brain

@article{Murthy2008InVC,
  title={In Vivo Characterization of a Novel Phenylisothiocyanate Tropane Analog at Monoamine Transporters in Rat Brain},
  author={V. Murthy and Thomas J Martin and Susy A. Kim and Huw M. L. Davies and Steven R. Childers},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2008},
  volume={326},
  pages={587 - 595}
}
Previous studies have shown that the phenylisothiocyanate tropane analog 2-β-propanoyl-3-β-(2-naphthyl)-8-[4-isothiocyanato)benzyl]nortropane (HD-205) binds covalently to dopamine and serotonin transporters (DAT and SERT, respectively) in rat brain membranes (Biochem Pharmacol 74:336–344, 2007). The present study evaluated the irreversible effects of HD-205 in vivo in rats after intracranial injection. Rats were implanted with unilateral cannulae in rat striatum, and HD-205 (0.001–3 nmol) was… Expand
Azido-iodo-N-benzyl derivatives of threo-methylphenidate (Ritalin, Concerta): Rational design, synthesis, pharmacological evaluation, and dopamine transporter photoaffinity labeling.
TLDR
Compound (±)-3a represents the first successful example of a DAT photoaffinity ligand based on the methylphenidate scaffold and is expected to assist in mapping non-tropane ligand-binding pockets within plasma membrane monoamine transporters. Expand
Effect of a chronic treatment with an mGlu5 receptor antagonist on brain serotonin markers in parkinsonian monkeys
TLDR
Investigation of the long-term effect of the prototypal metabotropic glutamate 5 (mGlu5) receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) with L-DOPA with MPEP found reduction of development of LID was associated with lower striatal and pallidal 5-HT2A receptors showing that glutamate activity also affects serotoninergic markers. Expand
Estradiol and brain serotonin reuptake transporter in long-term ovariectomized parkinsonian monkeys
TLDR
17β-estradiol treatment initiated four years after ovariectomy of monkeys modeling hormonal conditions of post-menopause shows that SERT still displays some responsiveness to estrogens as observed in the anterior cingulate cortex. Expand
Oestradiol Modulation of Serotonin Reuptake Transporter and Serotonin Metabolism in the Brain of Monkeys
TLDR
A significant positive correlation was observed between [3H]citalopram‐specific binding and 5‐HT concentrations in the caudate nucleus, putamen and nucleus accumbens, suggesting their link and have translational value for women with low oestrogen. Expand
Mineral Arsenicals in Traditional Medicines: Orpiment, Realgar, and Arsenolite
TLDR
Toxicological studies show that cardiovascular toxicity is the major concern for arsenic trioxide and that the gastrointestinal and dermal adverse effects may occur after prolonged use of mineral arsenicals, and total arsenic content alone appears to be insufficient for mineral arsenical safety evaluation. Expand

References

SHOWING 1-10 OF 69 REFERENCES
Irreversible binding of a novel phenylisothiocyanate tropane analog to monoamine transporters in rat brain.
TLDR
The results demonstrate that phenylisothiocyanate analogs of WF-23 can be used as potential ligands to map distinct binding sites of cocaine analogs at DAT. Expand
Characterization of a tropane radioligand, [(3)H]2beta-propanoyl-3beta-(4-tolyl) tropane ([(3)H]PTT), for dopamine transport sites in rat brain.
TLDR
Although the ability of various transporter inhibitors to displace both [(125)I]RTI-55 and [(3)H]PTT binding correlated significantly with each other, there was a better correlation of inhibitor potencies versus [(3]H] PTT binding and dopamine uptake than versus [(125). Expand
Dual incorporation of photoaffinity ligands on dopamine transporters implicates proximity of labeled domains.
TLDR
Results suggest that the two domains may be in close three-dimensional proximity and contribute to binding of multiple uptake blockers and reflect antagonist-induced conformational changes in the loop related to transport inhibition. Expand
Long-acting blockade of biogenic amine transporters in rat brain by administration of the potent novel tropane 2beta-propanoyl-3beta-(2-Naphthyl)-tropane.
TLDR
The slow onset and very long duration of action of WF-23, taken together with its actions at dopamine and serotonin transporters, suggest a potential role for treatment of disorders characterized by their involvement of these neural systems. Expand
Radioiodinated azide and isothiocyanate derivatives of cocaine for irreversible labeling of dopamine transporters: synthesis and covalent binding studies.
TLDR
The utility of the radioligands was demonstrated by their covalent linkage to rat striatal membranes, and immunoprecipitation of a single radiolabeled band at 80 kDa corresponding to the full-length DAT. Expand
Recovery of dopamine transporter binding and function after intrastriatal administration of the irreversible inhibitor RTI-76 [3 beta-(3p-chlorophenyl) tropan-2 beta-carboxylic acid p-isothiocyanatophenylethyl ester hydrochloride].
TLDR
The RTI-76-induced decrease in Bmax, as well as the concurrent decrease in [3H]DAT, were reversible, with the T1/2 of transporter recovery estimated to be 6 days, indicating at least some selectivity of RTi-76 for DAT. Expand
Time-Dependent Changes in Receptor/G-Protein Coupling in Rat Brain following Chronic Monoamine Transporter Blockade
TLDR
The time course of desensitization of monoamine receptor-coupled G-proteins in brain following chronic treatment of rats with WF-23 varied with different receptors, suggesting a role of D2 desensItization in producing tolerance to Wf-23-mediated behavior. Expand
Labeling of Dopamine Transporter Transmembrane Domain 1 with the Tropane Ligand N-[4-(4-Azido-3-[125I]iodophenyl)butyl]-2β-carbomethoxy-3β-(4-chlorophenyl)tropane Implicates Proximity of Cocaine and Substrate Active Sites
TLDR
The results directly establish the proximity of TMs 1 and 6 in DAT and suggest that the mechanism of transport inhibition by cocaine involves close interactions with multiple regions of the substrate permeation pathway. Expand
Novel 2-substituted cocaine analogs: binding properties at dopamine transport sites in rat striatum.
TLDR
A novel scheme utilizing vinylcarbenoid precursors has been developed for the synthesis of novel tropane analogs of cocaine, and the most potent analog was a 2-naphthyl derivative. Expand
Novel 2-substituted cocaine analogs: uptake and ligand binding studies at dopamine, serotonin and norepinephrine transport sites in the rat brain.
TLDR
The results suggest that large variations in the tropane structure do not result in a differentiation between binding at biogenic amine transporters and inhibition of amine uptake. Expand
...
1
2
3
4
5
...