The Anti-obesity Agent d-norpseudoephedrine Protects Against Rotenone-induced Parkinson’s Disease in Mice

Abstract

The effect of the ephedrine derivative D-norpseudoephedrine on rotenone-induced Parkinson’s disease in mice was studied. Mice received subcutaneous injections of rotenone (1.5 mg/kg, every other day for two weeks) and were treated with the vehicle, L-dopa (25 mg/kg) or pseudoephedrine at doses of 1.8, 5.4 and 10.8 mg/kg once daily orally. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) were determined and histopathological study of the brain was done. Motor testing included stair, wire hanging and wood walking tests. Results indicated that ompared with vehicle controls, rotenone caused significant increases in brain MDA and NO along with GSH depletion. Rotenone impaired neuromuscular strength, and motor balance and coordination. There were also marked decrease in size and number of substantia nigra pigmented cells and deeply stained neurons and karyorrhexis in the cerebral cortex and hippocampus. Treatment with pseudoephedrine reduced brain MDA, NO and increased GSH levels and improved motor performance. Furthermore, pseudoephedrine prevented substantia nigra dopaminergic cell death and neurodegeneration in the cortex and hippocampus brain regions in a dose-dependent manner. These data suggest that pseudoephedrine might prove of benefit adjunctive therapy of Parkinson’s disease.