Abstract
A series of para-substituted 4-phenylpiperidines/piperazines have been synthesized and their affinity to recombinant rat cerebral cortex monoamine oxidases A (MAO A) and B (MAO B) determined. Para-substituents with low dipole moment increased the affinity to MAO A, whereas groups with high dipole moment yielded compounds with no or weak affinity. In contrast, the properties affecting MAO B affinity were the polarity and bulk of the para-substituent, with large hydrophobic substituents producing compounds with high MAO B affinity. In addition, these compounds were tested in freely moving rats and the effect on the post-mortem neurochemistry was measured. A linear correlation was demonstrated between the affinity for MAO A, but not MAO B, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) in the striatum.
© 2012 American Chemical Society
MeSH terms
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3,4-Dihydroxyphenylacetic Acid / metabolism
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Animals
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Benzene Derivatives / chemical synthesis*
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Benzene Derivatives / chemistry
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Benzene Derivatives / pharmacology
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Catalytic Domain
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Corpus Striatum / drug effects
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Corpus Striatum / enzymology
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Dopamine / analogs & derivatives
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Dopamine / metabolism
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Humans
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Isoenzymes / metabolism
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Models, Molecular
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Monoamine Oxidase / metabolism
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Monoamine Oxidase Inhibitors / chemical synthesis*
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Monoamine Oxidase Inhibitors / chemistry
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Monoamine Oxidase Inhibitors / pharmacology
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacology
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Rats
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Structure-Activity Relationship
Substances
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Benzene Derivatives
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Isoenzymes
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Monoamine Oxidase Inhibitors
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Piperazines
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Piperidines
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3,4-Dihydroxyphenylacetic Acid
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Monoamine Oxidase
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3-methoxytyramine
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Dopamine