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Neuropharmacology. 2016 Mar;102:186-96. doi: 10.1016/j.neuropharm.2015.07.039. Epub 2015 Sep 25.

A heterocyclic compound CE-103 inhibits dopamine reuptake and modulates dopamine transporter and dopamine D1-D3 containing receptor complexes.

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Department of Paediatrics, Medical University of Vienna, 1090 Vienna, Austria.
Institute of Pharmacology, Centre of Physiology and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria.
Core Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Himberg, Austria.
TOSlab, Ural Federal University named after the first President of Russia, B. N. Yeltsin, Mira Str., 28, 620002 Yekaterinburg, Russia.
Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria. Electronic address:


A series of compounds have been reported to enhance memory via the DA system and herein a heterocyclic compound was tested for working memory (WM) enhancement. 2-((benzhydrylsulfinyl)methyl)thiazole (CE-103) was synthesized in a six-step synthesis. Binding of CE-103 to the dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters and dopamine reuptake inhibition was tested as well as blood brain permeation and a screen for GPCR targets. 60 male Sprague Dawley rats were divided into six groups: CE-103 treated 1-10 mg/kg body weight, trained (TDI) and yoked (YDI) and vehicle treated, trained (TVI) and yoked (YVI) rats. Daily single intraperitoneal injections for a period of 10 days were administered and rats were tested in a radial arm maze (RAM). Hippocampi were taken 6 h following the last day of training and complexes containing the unphosphorylated or phosphorylated dopamine transporter (DAT) and complexes containing the D1-3 dopamine receptor subunits were determined. CE-103 was binding to the DAT but insignificantly to SERT or NET and dopamine reuptake was blocked specifically (IC50 = 14.73 μM). From day eight the compound was decreasing WM errors in the RAM significantly at both doses tested as compared to the vehicle controls. In the trained CE-103-treated group levels of the complex containing the phosphorylated dopamine transporter (pDAT) as well as D1R were decreased while levels of complexes containing D2R and D3R were significantly increased. CE-103 was shown to enhance spatial WM and DA reuptake inhibition with subsequent modulation of D1-3 receptors is proposed as a possible mechanism of action.


CE-103; Cognitive enhancer; Dopamine receptors; Dopamine reuptake inhibitor; Radial arm maze; Working memory

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