Reduction of Nitroheterocyclic Drugs by Ascorbate and Catecholamines: A Possible Mechanism for the Neurotoxicity of Nitroheterocyclic Drugs
Nitroheterocyclic drugs such as 5-nitrofuran and 2- and 5-nitroimidazole derivatives are used as antimicrobial agents, some of which are selective for hypoxic cells.1 These compounds are also used as radiation sensitizers,2 and the 2-nitroimidazole derivative misonidazole was tested clinically. Unfortunately, a dose of 14 g/m2 needed to obtain sufficient tissue levels of this drug for sensitization produced a high incidence of peripheral neuropathy,3 hence this drug is of limited use.3 Nitrofurantoin and metronidazole also produce neuropathy.4,5 At lower doses nitrofurantoin is used as a urinary antiseptic,6 while metronidazole is used for amebic dysentery and for microbial infections of the vagina.7
KeywordsElectron Spin Resonance Electron Spin Resonance Spectrum Nitro Compound Mandelic Acid Semiquinone Radical
Unable to display preview. Download preview PDF.
- 1.R. P. Mason and P. D. Josephy, Free radical mechanism of nitroreductase, in: “Toxicity of Nitroaromatic Compounds,” D.E. Rickert, ed. Hemisphere Publishing Corp., Washington (1985).Google Scholar
- 2.A. Breccia and J. F. Fowler, “New Chemo and Radiosensitizing Drugs,” Edizioni Scientifiche (Lo Scarabeo), Bologna, Italy (1985).Google Scholar
- 3.T. Girinski, M. H. Pejovic, C. Haie, M. Bonnay, A. Gerbaulet, J. J. Mazeron, E. Malaise, and D. Chassagne, Radical irradiation and misonidazole in the treatment of advanced cervical carcinoma: Results of a phase II trial, Int. J. Radiat. Oncol. Biol. Phys. 11:1783 (1985).PubMedCrossRefGoogle Scholar
- 17.A. Motten and J. Schreiber, Correlation analysis of ESR spectra on a small computer, J. Magn. Reson. 67:42 (1986).Google Scholar