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A New Class of Monoamine Oxidase Inhibitors
Author(s) -
Vunnam R. R.,
Bond D.,
Schatz R. A.,
Radin N. S.,
Narasimhachari N.
Publication year - 1980
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1980.tb06611.x
Subject(s) - monoamine oxidase , enzyme , monoamine oxidase b , chemistry , substrate (aquarium) , ketone , stereochemistry , serotonin , in vivo , active site , covalent bond , biochemistry , biology , organic chemistry , ecology , receptor , microbiology and biotechnology
Newly synthesized compounds have been found to inhibit mitochondrial monoamine oxidase (MAO) in mouse brain and rat liver. A series of 2‐acylamino‐3‐ tert ‐aminopropiophenones acted preferentially against MAO type B (2‐phenylethylamine as substrate), apparently irreversibly. 2‐Decanoylamino‐3‐morpholinopropiophenone acted similarly in vivo toward the cerebral MAO, producing a dose‐related inhibition. At high dose levels, MAO type A was also severely inhibited. The effects were produced rapidly and restoration of enzyme activity also appeared rapidly. The half‐life for MAO type A could be estimated from the rate of enzyme reappearance to be 13 h. It is suggested that the amino ketones undergo a β‐elimination reaction at the enzyme's active site, forming a reactive species (an α,β‐unsaturated ketone), which reacts covalently with a nucleophilic group of the enzyme by a Michael addition. Some other related compounds, derivatives of phenylpropane, also showed inhibitory activity against MAO, particularly against type A (serotonin as substrate). The morpholino compound might have promise as a quickly effective, short‐acting inhibitor of MAO type B.