[125I]RTI-55: a potent ligand for dopamine transporters

Boja, John W.; Patel, Amrat; Carroll, F. Ivy; Rahman, Mostafizur; Abraham, Philip; Lewin, Anita H.; Kopajtic, T. A.; Kuhar, Michael J.

doi:10.1016/0014-2999(91)90137-f

Cited by 123 publications

(69 citation statements)

References 4 publications

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“…Affinities of analogs at DAT were determined by displacement of [ 125 I]RTI-55 binding in rat striatal membranes [11]. Frozen male rat brains were thawed on ice and striata were dissected.…”

Section: Binding Studiesmentioning

confidence: 99%

“…Development of novel cocaine analogs has two purposes: first, as potential therapeutic agents to treat cocaine abuse; second, as ligands to probe the structure of cocaine binding site on monoamine transporters. Numerous cocaine analogs have been studied in vivo, and several compounds are reported to attenuate cocaine's effects in animal models of psychomotor stimulant abuse [6,11]. Some of these have been evaluated preclinically and several are in clinical trials [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…Some of these have been evaluated preclinically and several are in clinical trials [12,13]. Radioligands synthesized from these compounds have been effective in vitro ligands for transporter binding [11,14,15] as well as PET ligands for in vivo imaging [16][17][18]. Furthermore, the structure-activity relationships of cocaine analogs have provided vital information to design specific molecular tools to characterize the structure and function of DAT, and to further explore its role in the pharmacology of cocaine.…”

Section: Introductionmentioning

confidence: 99%

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Irreversible binding of a novel phenylisothiocyanate tropane analog to monoamine transporters in rat brain

Murthy

Davies

Hedley

et al. 2007

Biochemical Pharmacology

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Irreversible tropane analogs have been useful in identifying binding sites of cocaine on biogenic amine transporters, including transporters for dopamine (DAT), serotonin (SERT) and norepinephrine (NET). The present study characterizes the properties of the novel phenylisothiocyanate tropane HD-205, synthesized from the highly potent 2-napthyl tropane analog WF-23. [ 125 I]HD-244 was synthesized with chloramine-T, purified on HPLC, reacted with rat striatal membranes, and proteins were separated by SDS-PAGE. Results showed several non-specific labeled bands, but only a single specific band of radioactivity co-migrating with an immunoreactive DAT band at approx. 80 kDa was detected, suggesting that [ 125 I]HD-244 covalently labeled DAT protein in striatal membranes. These results demonstrate that phenylisothiocyanate analogs of WF-23 can be used as potential ligands to map distinct binding sites of cocaine analogs at DAT.

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Section: Binding Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Irreversible binding of a novel phenylisothiocyanate tropane analog to monoamine transporters in rat brain

Murthy

Davies

Hedley

et al. 2007

Biochemical Pharmacology

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“…These analogs have made important contributions to understanding the role of DAT in mediating cocaine actions. For example, some tropane analogs have been used as radioligands at monoamine transporters, both in vitro (Boja et al, 1991a;Letchworth et al, 2000) and in vivo (Spencer et al, 2007). Other studies have focused on acute (Daunais et al, 1998) and chronic (Porrino et al, 1994;Hemby et al, 1995;O'Connor et al, 2004 effects of tropane analogs as psychostimulants, and several analogs have been reported to attenuate the effects of cocaine in animal models of psychostimulant abuse (Desai et al, 2005;Carroll et al, 2006).…”

mentioning

confidence: 99%

“…In autoradiography experiments, triplicate sections of brain from at least five animals were used for each assay. DAT binding was performed using [ 125 I]RTI-55 (Boja et al, 1991a), with fluoxetine to block binding of […”

mentioning

confidence: 99%

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

Murthy

Martin²,

Kim³

et al. 2008

J Pharmacol Exp Ther

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Previous studies have shown that the phenylisothiocyanate tropane analog 2-␤-propanoyl-3-␤-(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 administered by intrastriatal injection. 35 S]thio)-triphosphate binding in sections from the same animals. In a time course study, rats administered with 1 nmol HD-205 showed recovery of 50% DAT binding after 3 to 4 days postinjection, and full recovery after 6 weeks. Rats implanted with bilateral cannulae were tested for cocaine-induced locomotor activity. Two days after intrastriatal injection of 1 nmol of HD-205, systemic (20 mg/kg i.p.) cocaine-induced locomotor activity was not affected; however, locomotor activity induced by intrastriatal administration of cocaine (6 nmol) was eliminated. This strategy of site-specific chemical blockade of transporters could serve as a valuable tool to evaluate the neuroanatomical basis of DAT-mediated cocaine effects.Although cocaine binds to dopamine, serotonin, and norepinephrine transporters (DAT, SERT, and NET, respectively) with approximately equal affinities, it is hypothesized that an increase in extracellular dopamine levels due to blockade of DAT is responsible for its psychostimulant properties (Ritz et al., 1987). The role of DAT in these effects has been studied in DAT knockout mice, which exhibit both a higher level of baseline locomotor activity, as well as a blockade of cocaine-induced locomotor activity (Rocha et al., 1998;Carboni et al., 2001). Recent behavioral studies using a mutant DAT knock-in mouse strategy eliminated cocaine effects of locomotor activity and conditioned place preference (Chen et al., 2006). Therefore, DAT is a primary target to study the mechanisms involved in the psychostimulant properties of cocaine, and it serves as a target for development of therapeutic agents to treat cocaine addiction.Various structure-activity studies have resulted in the synthesis of cocaine analogs with differing affinities and selectivities at monoamine transporters (Boja et al., 1990;Davies et al., 1993). These analogs have made important contributions to understanding the role of DAT in mediating cocaine

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Endogenously released dopamine inhibits the binding of dopaminergic PET and SPECT ligands in superfused rat striatal slices

Gifford¹,

Gatley²,

Ashby³

1996

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[125I]RTI-55: a potent ligand for dopamine transporters

Cited by 123 publications

References 4 publications

Irreversible binding of a novel phenylisothiocyanate tropane analog to monoamine transporters in rat brain

Irreversible binding of a novel phenylisothiocyanate tropane analog to monoamine transporters in rat brain

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

Endogenously released dopamine inhibits the binding of dopaminergic PET and SPECT ligands in superfused rat striatal slices

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