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Effects of the Ornithine Decarboxylase Inhibitors Dl-α-Difluoromethylornithine and α-Monofluoromethyldehydroornithine Methyl Ester Alone and in Combination with Suramin against Trypanosoma brucei brucei Central Nervous System Models
C. J. Bacchi
C. J. Bacchi
Haskins Laboratories and Department of Biology, Pace University, New York, New York 10038
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H. C. Nathan
H. C. Nathan
Haskins Laboratories and Department of Biology, Pace University, New York, New York 10038
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A. B. Clarkson Jr.
A. B. Clarkson Jr.
Department of Medical and Molecular Parasitology, New York University, New York, New York 10016
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E. J. Bienen
E. J. Bienen
Department of Medical and Molecular Parasitology, New York University, New York, New York 10016
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A. J. Bitonti
A. J. Bitonti
Merrell Dow Research Institute, Cincinnati, Ohio 45215
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P. P. McCann
P. P. McCann
Merrell Dow Research Institute, Cincinnati, Ohio 45215
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A. Sjoerdsma
A. Sjoerdsma
Merrell Dow Research Institute, Cincinnati, Ohio 45215
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Two ornithine decarboxylase inhibitors, DL-α-difluoromethylornithine (eflornithine; DFMO) and a-monofluoromethyldehydroornithine methyl ester (ΔMFMO·CH3) were compared in their ability to cure two distinct Trypanosoma brucei brucei central nervous system murine model infections. Both inhibitors cured the TREU 667 and LUMP 1001 isolates if used in combination with a single (20 mg/kg) injection of suramin, a trypanocide in current clinical use. The curative dose of ΔMFMO·CH3 in combination with suramin was 1.09 g/kg/day, administered in the drinking water for 14 days; used with suramin, the curative dose of DFMO was 5.3 g/kg/day for 14 days (5 times the ΔMFMO·CH3 dose required). In host animals, ΔMFMO·CH3 was not toxic and was accumulated by trypanosomes 6–8 times faster than DFMO. Since DFMO by itself has been highly effective against T. b. gambiense infections in humans (12–15 g/day for 6 weeks) the present data suggest that ΔMFMO·CH3 might be effective in a shorter regimen and at lower doses.
| Past two years | Past Year | Past 30 Days | |
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| Abstract Views | 249 | 92 | 4 |
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| PDF Downloads | 6 | 2 | 0 |