The interactions of milacemide with monoamine oxidase.

Abstract The interactions of the anticonvulsant drug milacemide (2- n -pentylaminoacetamide) with rat liver mitochondrial monoamine oxidases-A and -B have been studied. The compound acts as a substrate for the B-fonn of the enzyme, with an apparent K m value of 49 ± 4.7 μ M and a V max value of 1.1 ± 0.2 nmol/min/mg. It is also a time-dependent irreversible inhibitor of that enzyme. Any activity of monoamine oxidase-A towards this substrate was too low to allow accurate determinations to be made by either luminometric determination of H 2 O 2 formation or spectrophotometric coupling of aldehyde formation to NAD + reduction in the presence of aldehyde dehydrogenase. Milacemide was a reversible competitive inhibitor towards monoamine oxidase-A. The inhibitor constant ( K i was 115 ± 35 μ M indicating a higher affinity than that towards monoamine oxidase-B, which was also competitively inhibited in the absence of enzyme-inhibitor preincubation ( K i = 331 ± 185 μ M). Determination of the formation of H 2 O 2 and the aldehyde product of the oxidative cleavage of milacemide by purified monoamine oxidase-B from ox liver indicated that cleavage resulted solely in the formation of pentanal and glycinamide. There was no evidence for alternative cleavage to pentylamine and oxamaldehyde.