1-methyl-4-phenylpyridinium (MPP+) analogs: in vivo neurotoxicity and inhibition of striatal synaptosomal dopamine uptake.
The ability of various 1-methyl-4-phenylpyridinium (MPP+) analogs to inhibit the uptake of tritium labeled dopamine and MPP+ by synaptosomes prepared from neostriata of male C57 Black mice was measured and compared with their dopaminergic neurotoxic potential which was estimated by an in vivo intracerebral microdialysis technique. The correlation observed between these two properties suggests that nerve terminal uptake is an important step in the expression of the nigrostriatal toxicity of structural analogs of MPP+. The uptake inhibition and neurotoxic properties of this series of compounds appear to be highly structurally sensitive and suggest that few nitrogenous bases will be potent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-type neurotoxins.
Johnson
E A
EA
Department of Pharmaceutical Chemistry, University of California, San Francisco.
Wu
E Y
EY
Rollema
H
H
Booth
R G
RG
Trevor
A J
AJ
Castagnoli
N
N
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology* / Q000633:toxicity; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology* / Q000633:toxicity; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D009498:Neurotoxins; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine