Inhibition of MAO B, but not MAO A, blocks DSP-4 toxicity on central NE neurons.
The neurotoxin, DSP-4, (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) specifically and significantly reduces norepinephrine (NE) and its metabolite, 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), in cortical, hippocampal and cerebellar brain regions. Pretreatment with the selective monoamine oxidase (MAO) B inhibitor, deprenyl, and the non-specific MAO inhibitor, pargyline, effectively blocked NE depletion. Pretreatment with the selective MAO A inhibitor, clorgyline, had no effect on central NE DSP-4 toxicity. Thus formation of a toxic metabolite by the action of MAO B may be involved in DSP-4 induced neural damage.
D000818:Animals; D001596:Benzylamines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001923:Brain Chemistry / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009638:Norepinephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology
D001596:Benzylamines; D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D012642:Selegiline; D008734:Methoxyhydroxyphenylglycol; D010293:Pargyline; C012102:DSP 4; D009638:Norepinephrine