Synthesis and toxicity toward nigrostriatal dopamine neurons of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) analogues.
Six compounds having structural features in common with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and tested in mice for the ability to produce a prolonged decrease in nigrostriatal dopamine (DA) and DA metabolites. The compounds that were prepared and tested include the ester elimination products of the analgetic drugs alpha-prodine and trimeperidine. None of the compounds in this study, except for MPTP, produced significant neurotoxic effects in the mouse model. The study shows that minor changes in the tetrahydropyridine ring of MPTP result in a marked decrease in neurotoxicity.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis* / Q000633:toxicity; D013329:Structure-Activity Relationship; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D011725:Pyridines; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid