Dopamine but not norepinephrine or serotonin uptake inhibitors protect mice against neurotoxicity of MPTP.
Combined administration of nomifensine, a DA reuptake inhibitor, and MPTP completely prevented the long-term (30 days post-treatment) striatal DA depletions induced by MPTP in mice. Cotreatment with desipramine and clomipramine or fluoxetine, inhibitors of NE and 5-HT, respectively had no effect on DA neurotoxicity of MPTP. The findings indicate that MPTP (or MPP+) is a substrate for the specific DA reuptake system and may explain, in part, its selective toxic effects on DA neurons.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002997:Clomipramine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009627:Nomifensine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D011725:Pyridines; D012702:Serotonin Antagonists; D005473:Fluoxetine; D009627:Nomifensine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002997:Clomipramine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine