Abstract |
1-Methyl-4-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridine (2) produced persistent depletion of striatal dopamine in mice after four daily injections, although it was less potent than 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP). MPTP has been implicated as a cause of Parkinsonism in drug abusers who inadvertently self-administered it and in industrial chemists who were exposed to it. Our results suggest that the m-methoxy compound has the same neurotoxic potential to cause destruction of nigrostriatal dopamine neurons that would lead to Parkinsonian symptoms in humans. In contrast, 1-ethyl-4-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridine (11) had no effects on striatal dopamine in mice, even at doses 8 times those of MPTP. A method of preparing 11 and using it as an intermediate in the synthesis of potential analgesic drugs, thus avoiding a potentially neurotoxic intermediate, is described.
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Authors | D M Zimmerman, B E Cantrell, J K Reel, S K Hemrick-Luecke, R W Fuller |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 29
Issue 8
Pg. 1517-20
(Aug 1986)
ISSN: 0022-2623 [Print] United States |
PMID | 3488406
(Publication Type: Journal Article)
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Chemical References |
- Pyridines
- 3,4-Dihydroxyphenylacetic Acid
- 1-ethyl-4-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridine
- 1-methyl-4-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridine
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- Dopamine
- Homovanillic Acid
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Topics |
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- 3,4-Dihydroxyphenylacetic Acid
(metabolism)
- Animals
- Brain
(drug effects)
- Corpus Striatum
(drug effects, metabolism)
- Dopamine
(metabolism)
- Homovanillic Acid
(metabolism)
- Mice
- Parkinson Disease, Secondary
(chemically induced)
- Pyridines
(chemical synthesis, pharmacology, toxicity)
- Structure-Activity Relationship
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