Monoamine oxidase and the bioactivation of MPTP and related neurotoxins: relevance to DATATOP.
The DATATOP study is a clinical trial in which deprenyl, a selective inhibitor of monoamine oxidase-B (MAO-B), is being given to newly diagnosed Parkinsonian patients in an attempt to halt the progression of their disorder. In part, this is being done because of the working hypothesis than an MPTP-like molecule may be the cause of Parkinsonism, and deprenyl is known to protect against MPTP-induced dopaminergic neurotoxicity in experimental animals. In the present study we point out that several analogs of MPTP are good substrates not only for MAO-B but also for MAO-A. In addition, we point out that with long-term administration to rodents, deprenyl loses its selectivity as an inhibitor of MAO-B and also inhibits MAO-A. We believe that these observations have relevance for the DATATOP study.
Heikkila
R E
RE
Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, Piscataway.
Terleckyj
I
I
Sieber
B A
BA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism*; D009420:Nervous System / Q000187:drug effects; D009498:Neurotoxins; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000378:metabolism*; D014810:Vitamin E / Q000378:metabolism*
D009498:Neurotoxins; D014810:Vitamin E; D012642:Selegiline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase