piperidines and 3-methoxytyramine

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.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Benzene Derivatives; Catalytic Domain; Corpus Striatum; Dopamine; Humans; Isoenzymes; Models, Molecular; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Piperazines; Piperidines; Rats; Structure-Activity Relationship