The effect of low oral doses of (−)-deprenyl and its metabolites on DSP-4 toxicity

Summary.

Treatment with a single oral dose of (−)-deprenyl (selegiline) before DSP-4 administration could dose-dependently decrease the noradrenaline (NA) depleting effect of the toxin in mouse hippocampus. The maximum protective effect was achieved at as low oral dose as 0.25 mg/kg. Pre-treatment with the same doses of the main metabolites of (−)-deprenyl: (−)-amphetamine and (−)-methylamphetamine provided a weaker attenuation of DSP-4 induced NA depletion, than the parent compound. The selective noradrenergic toxin DSP-4, which depletes NA in nerve terminals originating from the locus coeruleus, is presumably metabolised by CYP-450 enzymes. Continuous administration of low, by themselves non-toxic doses of DSP-4 resulted in the cumulation of its NA depleting effect.