The novel neuropsychotropic agent milacemide is a specific enzyme-activated inhibitor of brain monoamine oxidase B.
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, partially 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.
Searle European Development Centre, Continental Pharma, Inc., Mont-Saint-Guibert, Belgium.
P
P
Janssens de Varebeke
G
G
Pauwels
C
C
Buyse
M
M
David-Remacle
J
J
De Mey
J
J
Roba
M B
MB
Youdim
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000201:enzymology*; D003010:Clorgyline / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects*; D014439:Tyramine / Q000494:pharmacology
D000081:Acetamides; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; C039332:milacemide; D003010:Clorgyline; D014439:Tyramine