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- W2019179515 abstract "Both 3- and 4-substituted GBR 12783 derivatives were synthesized in an effort to create site-directed cocaine antagonists. The potencies of these compounds to inhibit stimulant ([3H]WIN 35,428) binding and synaptosomal [3H]dopamine uptake were determined and compared with a large number of compounds assayed under identical experimental conditions. Three groups of compounds were identified which affected stimulant binding and dopamine transport to varying degrees. The 3-substituted GBR 12783 derivatives resembled the known non-amphetamine stimulant agents, in that they were approximately equipotent in inhibiting [3H]WIN 35,428 binding and [3H]dopamine transport. The 4-substituted GBR 12783 derivatives formed a second group that was approximately seven times more potent in the inhibition of [3H]dopamine uptake compared to [3H]WIN 35,428 binding. The third group, approximately one hundred-fold more potent at inhibiting [3H]dopamine uptake than stimulant binding, consisted mainly of substrates for the dopamine transporter. Although these GBR derivatives did not meet the criteria for potential cocaine antagonists, the results demonstrate that slight modifications of the molecular structure of a stimulant drug can differentially affect binding and transport. This finding holds great promise for the eventual development of a true pharmacological antagonist of cocaine." @default.
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- W2019179515 date "1994-01-01" @default.
- W2019179515 modified "2023-10-16" @default.
- W2019179515 title "Can stimulant binding and dopamine transport be differentiated? Studies with GBR 12783 derivatives" @default.
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- W2019179515 doi "https://doi.org/10.1016/0024-3205(94)90061-2" @default.
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