AbstractRecent clinical studies suggest that selegiline (L‐deprenyl) is useful in retarding the progress of Parkinson's disease, an effect that may be related to its inhibition of monoamine oxidase type B (MAO‐B). Selegiline is also reported to prevent the toxic effects of the noradrenergic neurotoxin,N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine (DSP‐4). This article reviews recent studies on the role of MAO‐B and its inhibition in this neuroprotective action of selegiline. Male C57Bl/6 mice were given DSP‐4 (50 mg/kg) 1 h, 24 h, or 4 days after the administration of selegiline (10 mg/kg) or the selective MAO‐B inhibitor MDL 72974 (1.25 mg/kg) and then killed 1 week later for the assay of norepinephrine in hippocampus. The MAO‐B‐inhibiting effects of selegiline or MDL 72974 were also determined after these same intervals. Selegiline and MDL 72974 produced comparable degrees of enzyme inhibition 1 h (>95%), 24 h(>90%), or 4 days (>70%) after their administration. Given 1 h before, selegline totally bloked the norepinephrinedepleting effects of DSP‐4, but this protection declined sharply when 24 h or 4 days was allowed to elapse between selegiline and DSP‐4 administration. MDL 72974 failed to protect at any time point. In vitro, no activity was observed when DSP‐4 was used as a substrate for MAO. All of these findings suggest that the ability of selegiline to protect against DSP‐4‐induced neuronal degeneration does