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The Novel Neuropsychotropic Agent Milacemide Is a Specific Enzyme‐Activated Inhibitor of Brain Monoamine Oxidase B
Author(s) -
Varebeke Philippe Janssens,
Pauwels Gilbert,
Buyse Corinne,
DavidRemacle Michele,
Mey Jo De,
Roba Josd,
Youdim Moussa B. H.
Publication year - 1989
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.1471-4159.1989.tb07403.x
Subject(s) - monoamine oxidase b , monoamine oxidase , in vivo , pharmacology , tyramine , selegiline , chemistry , dopaminergic , monoamine oxidase a , dopamine , inhibitory postsynaptic potential , enzyme , biochemistry , biology , parkinson's disease , endocrinology , medicine , microbiology and biotechnology , disease
The novel neuropsychotropic agent milacemide hydrochloride (2‐ n ‐pentylaminoacetamide HCl) is a highly selective substrate of the B form of monoamine oxidase (EC 1.4.3.4; MAO). Under the in vitro conditions used in the present study, milacemide acts as an enzyme‐activated, par‐tially reversible inhibitor of MAO‐B. A reversible inhibition of MAO‐A activity is also observed at high concentrations. The inhibitory activity of milacemide is significantly greater for MAO‐B. In vivo, after single or repeated oral administration, a specific inhibition of MAO‐B is apparent in brain and liver, with a lack of inhibition of the MAO‐A Activity. In contrast to the irreversible inhibitory action of L‐deprenyl, the recovery of MAO‐B activity in vivo after milacemide administration is significantly faster, a result suggesting that it is a partially reversible inhibitor. The selective inhibitory effect of milacemide for MAO‐B in vivo is confirmed by its potentiation of phenylethylamine‐induced stereotyped behavior, whereas vasopressor responses to tyramine were not affected. These observations suggest that milacemide could enhance dopaminergic activity in the brain and could be used as therapy for Parkinson's disease in association with L‐3,4‐dihydroxyphenylalanine.