Neurotoxicity of misonidazole in rats. I. Neuropathology

Misonidazole is a 2-nitroimidazole compound developed as a hypoxic cell sensitizer for cancer radiotherapy. Because neurotoxicity has occurred in clinical trials, we have examined the neuropathology of intoxicated rats. In the peripheral nervous system, changes consisted of distal axonal degeneration in intramuscular nerve branches, and edema in dorsal root ganglia. In the central nervous system, spongy changes were found in the lateral and superior vestibular nuclei, the superior olives, and often in the cochlear nuclei and cerebellar roof nuclei. In advanced lesions these structures underwent necrosis and scattered petechiae were found around the IVth ventricle. The pathology resembled that associated with thiamine deficiency in the rat.