Selective inactivation of MAO-B by benzyl-dimethyl-silyl-methanamines in vitro.
The alpha-silyl amines benzyl-dimethyl-silyl-methanamine and the p-fluoro and p-chloro derivatives are potent time-dependent inhibitors of rat brain MAO-B. The inhibition exhibits saturation kinetics, takes place in the enzyme active-site and is irreversible. The most potent inhibitor in the series is 4-fluorobenzyl-dimethyl-silyl-methanamine (KI = 11 microM, tau 1/2 = 2.3 min). Its selectivity for the B-form relative to the A-form of rat brain MAO is higher than 10(4). Benzyl-dimethyl-silyl-methanamines may represent a new family of anti-Parkinsonian agents.
Danzin
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Merrell Dow Research Institute, Strasbourg, France.
Collard
J N
JN
Marchal
P
P
Schirlin
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D
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D008744:Methylamines / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D012825:Silicon / Q000494:pharmacology*; D013379:Substrate Specificity
D001596:Benzylamines; D008744:Methylamines; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D012825:Silicon