The effect of low oral doses of (-)-deprenyl and its metabolites on DSP-4 toxicity.
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.
Haberle
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Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
Szökö
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Halász
A S
AS
Magyar
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K
D000284:Administration, Oral; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000378:metabolism; D001596:Benzylamines / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism; D012642:Selegiline / Q000008:administration & dosage* / Q000378:metabolism*
D000978:Antiparkinson Agents; D001596:Benzylamines; D008996:Monoamine Oxidase Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D012642:Selegiline; C012102:DSP 4; D009638:Norepinephrine