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MDL 72145, an Enzyme‐Activated Irreversible Inhibitor with Selectivity for Monoamine Oxidase Type B
Author(s) -
Zreika Monique,
McDonald Ian A.,
Bey Philippe,
Palfreyman Michael G.
Publication year - 1984
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.1471-4159.1984.tb00920.x
Subject(s) - monoamine oxidase , monoamine oxidase b , enzyme , benzylamine , chemistry , selectivity , stereochemistry , hydrochloride , in vitro , biochemistry , selegiline , monoamine oxidase a , clorgyline , medicinal chemistry , catalysis , medicine , disease , parkinson's disease
MDL 72145, ( E )‐2‐(3′,4′‐dimethoxyphenyl)‐3‐fluoroallylamine hydrochloride, was designed and synthesised as a potential enzyme‐activated irreversible inhibitor of monoamine oxidase (MAO). In vitro , the compound displayed time‐dependent pseudo‐first‐order irreversible inhibitory characteristics with high selectivity for the B form of rat brain mitochondrial MAO At 10°C the K t and T 50 values for the B enzyme were 40 μ M and 1.7 min, respectively, while these same kinetic constants for the A enzyme were 131 μ M and 14.5 mm, respectively. Selective protection against inactivation of the two forms of MAO by MDL 72145 was obtained by preincu‐bating the enzyme with suitable concentrations of the selective A and B substrates, 5‐hydroxytryptamine and benzylamine.