Studies on 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine, a nonneurotoxic analog of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
| Autor: | Hans Rollema, Elizabeth Johnson, Neal Castagnoli, Noreen Naiman |
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| Rok vydání: | 1990 |
| Předmět: |
Microdialysis
Metabolite Mitochondria Liver Pharmacology Toxicology chemistry.chemical_compound In vivo Dopamine Cricetinae medicine Animals Neurotoxin Parkinson Disease Secondary Monoamine Oxidase MPTP Neurotoxicity Brain MPTP Poisoning General Medicine medicine.disease Rats Liver chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Cattle Monoamine oxidase B Oxidation-Reduction medicine.drug |
| Zdroj: | Chemical Research in Toxicology. 3:133-138 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx00014a008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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