Different neurorescue profiles of selegiline and p-fluoro-selegiline in gerbils

The neuroprotective/neuronal rescue effects of selegiline are not exactly u nderstood, and show great variability in clinical trials. In this study, th e dose-dependence of neuronal rescue potency of selegiline and its analogue para-fluoro-selegiline (PFS) was investigated in gerbils. The compounds we re tested in a transient global cerebral ischemia model. Selegiline express ed a bell-shaped, dose-response curve with high intrinsic activity (with gr eatest effect at 0.001 mg/kg), as opposed to PFS which shows a saturation p rofile. These findings indicate possible therapeutic differences between PF S and selegiline in the treatment of neurodegenerative disorders. Inhibitio n of progression of the disease (neuroprotective effect) and improvements o f symptoms (MAO-B inhibition) may occur at the same dose level using PFS, w hile these doses are separated in case of selegiline. NeuroReport 11:2597-2 600 (C) 2000 Lippincott Williams & Wilkins.