MDL 72145, an Enzyme-Activated Irreversible Inhibitor with Selectivity for Monoamine Oxidase Type B

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Abstract
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 Kt and T50 values for the B enzyme were 40 μM and 1.7 min, respectively, while these same kinetic constants for the A enzyme were 131 μM 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.