Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Antiparkinson Agents / administration & dosage
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Antiparkinson Agents / metabolism
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Benzylamines / administration & dosage
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Benzylamines / toxicity*
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Hippocampus / drug effects
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Hippocampus / metabolism
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Injections, Intraperitoneal
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Male
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Mice
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Monoamine Oxidase Inhibitors / administration & dosage
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Monoamine Oxidase Inhibitors / metabolism
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Neurotransmitter Uptake Inhibitors / administration & dosage
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Neurotransmitter Uptake Inhibitors / toxicity*
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Norepinephrine / metabolism
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Selegiline / administration & dosage*
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Selegiline / metabolism*
Substances
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Antiparkinson Agents
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Benzylamines
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Monoamine Oxidase Inhibitors
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Neurotransmitter Uptake Inhibitors
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Selegiline
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DSP 4
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Norepinephrine