Abstract:
:Previous reports indicate that 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine (BMTP), the benzyl analogue of the Parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is not neurotoxic in the C-57 black mouse even when administered at a dose 10 times greater than the dose of MPTP required to cause an 85% depletion of neostriatal dopamine. Intrastriatal microdialysis in the rat with the corresponding 4-benzyl-1-methylpyridinium ion BMP+ for 60 min, however, causes nerve terminal destruction similar to that observed following a 15-min perfusion with the 1-methyl-4-phenylpyridinium ion MPP+, the monoamine oxidase B (MAO-B) generated metabolite derived from MPTP. With the aid of purified beef liver MAO-B and synthetic standards, we observed the efficient and quantitative conversion of BMTP to the corresponding 2,3-dihydropyridinium intermediate BMDP+, which underwent further, but incomplete, oxidation to BMP+. These MPTP-type properties point to in vivo effects, such as pharmacokinetic parameters and/or alternative metabolic pathways, to account for BMTP's lack of neurotoxicity.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Naiman N,Rollema H,Johnson E,Castagnoli N Jrdoi
10.1021/tx00014a008subject
Has Abstractpub_date
1990-03-01 00:00:00pages
133-8issue
2eissn
0893-228Xissn
1520-5010journal_volume
3pub_type
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