Milacemide: a neuropsychotropic glycine prodrug that potentiates serotonergic activity

Moussa B. H. Youdim

in 5-Hydroxytryptamine in Psychiatry

Published in print February 1991 | ISBN: 9780192620118
Published online March 2012 | e-ISBN: 9780191724725 | DOI:
Milacemide: a neuropsychotropic glycine prodrug that potentiates serotonergic activity

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Milacemide is the first glycine prodrug which, unlike the inhibitory neurotransmitter, glycine can readily cross the blood–brain border. In the brain, glycineamide and glycine are the major metabolites of milacemide. It is now apparent that the formation of glycine and the antiseizure action of milacemide are dependent on the activity of brain monoamine oxidase B (MAO-B), for which milacemide is a selective substrate in vitro and in vivo. Thus, in hyperbaric oxygen-induced seizure, the selective MAO-B inhibition by L-deprenyl, rather than inhibition of MAO-A by clorgyline, prevents the milacemide-induced increase in seizure latency. Therefore, milacemide's anticonvulsant property has been attributed to the formation of its major metabolites — pentanoic acid, glycineamide, and glycine — by the oxidative reaction of MAO-B. Milacemide is also an enzyme-activated specific inhibitor of MAO-B. In vitro and in vivo studies confirm these findings. This study has demonstrated another pharmacological property of milacemide — its ability to potentiate serotonin neurotransmission-dependent behaviour in rats in a dose-dependent fashion.

Keywords: milacemide; glycine; blood–brain border; glycineamide; monoamine oxides; L-deprenyl; seizure latency

Chapter.  2187 words.  Illustrated.

Subjects: Neuroscience

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