• 대한방사성의약품학회지
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• 제3권1호
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• pp.32-37
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• 2017

Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tertrahydro-N-methyl-1-naphthalenamine (sertraline) hydrochloride from among selective serotonin reuptake inhibitors (SSRIs) is a treatment of major depression. For the differential diagnosis by metabolizing serotonin in a patient with neurological disorders, the radiolabeled $^{11}C$-sertraline was developed for non-invasive positron emission tomography in living brain and use the evaluation of new drug for SSRIs. We release the results of a fast and easy radiolabeling method applied a one-step loop method with $[^{11}C]CH_3OTf$ for routine clinical applications of $^{11}C$-sertraline. 1 mg of a precursor for $^{11}C$-sertraline in 0.1 mL DMF and $5{\mu}L$ of 1N NaOH, were injected into the loop of semi-prep high-performance liquid chromatography (HPLC). $[^{11}C]CH_3OTf$ was passed through the loop at room temperature (RT). The $^{11}C$-sertraline was separated by the semi-preparative HPLC. $^{11}C$-sertraline was eluted at 28.0 min was collected and evaluated by analytical HPLC and mass spectrometer. The total radiolabeling efficiency of $^{11}C$-sertraline was $30.7{\pm}8.7%$. The specific activity was $64.8{\pm}51.4GBq/{\mu}mol$. The radiochemical and chemical purities were higher than 99%. The mass spectrum of the product showed m/z peaks at 307.1 (M+1), indicating the mass of sertraline. By the one-step loop method with $[^{11}C]CH_3OTf$, $^{11}C$-sertraline could be quickly and easily prepared for clinical application.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.78-83
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• 2005

2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) has previously shown to induce neurotoxicity through intracellular $Ca^{2+}$ increase in rat neurons. In this study we investigated the role and signaling pathway of intracellular $Ca^{2+}$ in TCDD-induced inhibition of neuronal cell proliferation in SK-N-SH human neuronal cells. We found that TCDD(10nM) rapidly increased the level of intracellular $Ca^{2+}$, which was completely blocked by the extracellular $Ca^{2+}$ chelation with EGTA (1 mM) or by pretreatment of the cells with the non-selective cation channel blocker. flufenamic acid (200 ${\mu}M$). However, pretreatment of the cells with dantrolene (25 ${\mu}M$) and TMB-8(10 ${\mu}M$), intracellular $Ca^{2+}$-release blockers, or a voltage-sensitive $Ca^{2+}$ channel blocker, varapamil (100 ${\mu}M$), failed to block the TCDD-induced $Ca^{2+}$ increase in the cells. In addition, TCDD induced a rapid and transient activation of phatidvlinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2(ERK1/2), which was ingnificantly blocked by the pretreatment with BAPTA, an intracellular $Ca^{2+}$ chelator, and LY294002, a PI3K inhibitor. Furthermore, inhibitors of PI3K, ERK, or an intracellular $Ca^{2+}$ chelator further potentiated the anti-proliferative effect of TCDD in the cells. Collectively, the results suggest that intracellular $Ca^{2+}$ and PI3K-dependent activation of ERK 1/2 may be involved in the TCDD-induced inhibition of cell proliferation in SK-N-SH human neuronal cells.

• The Korean Journal of Physiology and Pharmacology
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• 제16권3호
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• pp.181-186
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• 2012

Fenofibrate is a selective peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) activator and is prescribed to treat hyperlipidemia. The mechanism through which $PPAR{\alpha}$ agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.