The Experts below are selected from a list of 21 Experts worldwide ranked by ideXlab platform

M. E. Schweingruber - One of the best experts on this subject based on the ideXlab platform.

  • The antitrypanosomal drug melarsoprol competitively inhibits thiamin uptake in mouse neuroblastoma cells
    Cell Biology and Toxicology, 2006
    Co-Authors: P. Szyniarowski, L. Bettendorff, M. E. Schweingruber
    Abstract:

    Melarsoprol is the main drug used for the treatment of late-stage sleeping sickness, although it causes severe side-effects such as encephalopathy and polyneuropathy leading to death in some patients. Recent data suggest that melarsoprol and its active metabolite Melarsenoxide interfere with thiamin transport and metabolism in E. coli and yeast, but there are no data concerning their possible effects on thiamin metabolism in mammalian cells. We tested both drugs on thiamin transport in cultured mouse neuroblastoma cells using ^14C-labeled thiamin. Melarsoprol, competitively inhibits high-affinity thiamin transport in mouse neuroblastoma cells with a K _i of 44 μmol/L. However, the active compound Melarsenoxide has no inhibitory effect. This suggests that the side effects of melarsoprol treatment are unlikely to be due to inhibition of thiamin transport by Melarsenoxide, its main metabolite in the brain.

P. Szyniarowski - One of the best experts on this subject based on the ideXlab platform.

  • The antitrypanosomal drug melarsoprol competitively inhibits thiamin uptake in mouse neuroblastoma cells
    Cell Biology and Toxicology, 2006
    Co-Authors: P. Szyniarowski, L. Bettendorff, M. E. Schweingruber
    Abstract:

    Melarsoprol is the main drug used for the treatment of late-stage sleeping sickness, although it causes severe side-effects such as encephalopathy and polyneuropathy leading to death in some patients. Recent data suggest that melarsoprol and its active metabolite Melarsenoxide interfere with thiamin transport and metabolism in E. coli and yeast, but there are no data concerning their possible effects on thiamin metabolism in mammalian cells. We tested both drugs on thiamin transport in cultured mouse neuroblastoma cells using ^14C-labeled thiamin. Melarsoprol, competitively inhibits high-affinity thiamin transport in mouse neuroblastoma cells with a K _i of 44 μmol/L. However, the active compound Melarsenoxide has no inhibitory effect. This suggests that the side effects of melarsoprol treatment are unlikely to be due to inhibition of thiamin transport by Melarsenoxide, its main metabolite in the brain.

L. Bettendorff - One of the best experts on this subject based on the ideXlab platform.

  • The antitrypanosomal drug melarsoprol competitively inhibits thiamin uptake in mouse neuroblastoma cells
    Cell Biology and Toxicology, 2006
    Co-Authors: P. Szyniarowski, L. Bettendorff, M. E. Schweingruber
    Abstract:

    Melarsoprol is the main drug used for the treatment of late-stage sleeping sickness, although it causes severe side-effects such as encephalopathy and polyneuropathy leading to death in some patients. Recent data suggest that melarsoprol and its active metabolite Melarsenoxide interfere with thiamin transport and metabolism in E. coli and yeast, but there are no data concerning their possible effects on thiamin metabolism in mammalian cells. We tested both drugs on thiamin transport in cultured mouse neuroblastoma cells using ^14C-labeled thiamin. Melarsoprol, competitively inhibits high-affinity thiamin transport in mouse neuroblastoma cells with a K _i of 44 μmol/L. However, the active compound Melarsenoxide has no inhibitory effect. This suggests that the side effects of melarsoprol treatment are unlikely to be due to inhibition of thiamin transport by Melarsenoxide, its main metabolite in the brain.

Schweingruber M. E. - One of the best experts on this subject based on the ideXlab platform.

  • The antitrypanosomal drug melarsoprol competitively inhibits thiamin uptake in mouse neuroblastoma cells
    2006
    Co-Authors: Szyniarowski Piotr, Bettendorff Lucien, Schweingruber M. E.
    Abstract:

    Melarsoprol is the main drug used for the treatment of late-stage sleeping sickness, although it causes severe side-effects such as encephalopathy and polyneuropathy leading to death in some patients. Recent data suggest that melarsoprol and its active metabolite Melarsenoxide interfere with thiamin transport and metabolism in E. coli and yeast, but there are no data concerning their possible effects on thiamin metabolism in mammalian cells. We tested both drugs on thiamin transport in cultured mouse neuroblastoma cells using C-14-labeled thiamin. Melarsoprol, competitively inhibits high-affinity thiamin transport in mouse neuroblastoma cells with a K-i of 44 mu mol/L. However, the active compound Melarsenoxide has no inhibitory effect. This suggests that the side effects of melarsoprol treatment are unlikely to be due to inhibition of thiamin transport by Melarsenoxide, its main metabolite in the brain.Peer reviewe

Christian Burri - One of the best experts on this subject based on the ideXlab platform.

  • investigations of the metabolites of the trypanocidal drug melarsoprol
    Clinical Pharmacology & Therapeutics, 2000
    Co-Authors: Jennifer Keiser, Örjan Ericsson, Christian Burri
    Abstract:

    Background Melarsoprol remains the first-choice drug for trypanosomiasis (human African sleeping sickness). To contribute to the sparse pharmacologic data and to better understand the cause of the frequent serious adverse reactions, we investigated the metabolism of this 50–year-old organoarsenic compound. Results The half-life of melarsoprol determined by HPLC was <1 hour compared with 35 hours determined by bioassay and atomic absorption spectroscopy, indicating the existence of active metabolites. One metabolite, melarsen oxide, was identified by ultraviolet HPLC after incubation of melarsoprol with microsomes. The maximum plasma concentration of Melarsenoxide was reached 15 minutes after administration; the clearance was 21.5 mL/min/kg and the half-life of free melarsen oxide was 3.9 hours. Either melarsen oxide or a yet-undiscovered active metabolite is irreversibly bound to proteins, as shown by ultrafiltration, precipitation experiments, and atomic absorption spectroscopy. Because of the poor pharmaceutical properties of melarsoprol, the therapeutic potential of melarsen oxide was investigated. In a rodent model of acute infection, 20 of 20 mice were cured (0.1 to 1 mg/kg intravenously or 2.2 mg/kg intraperitoneally). In a rodent model of central nervous system infection, five of six mice survived for more than 180 days (5 mg/kg intravenously), indicating a sufficient melarsen oxide penetration across the blood-brain barrier. Conclusion The prospects for the future of trypanosomiasis treatment are deplorable. Investigations on the improvement of the use of the old drugs are therefore required. The results of this study may build a basis for further research on the cause of severe adverse reactions. Clinical Pharmacology & Therapeutics (2000) 67, 478–488; doi: 10.1067/mcp.2000.105990