Monoamine oxidase inhibitory properties of milacemide in rats.
Milacemide is a glycine prodrug with reported antiepileptic antimyoclonic properties. In this study, milacemide increased "wet dog shakes" in rats pretreated with 5-Hydroxytryptophan (5-HTP) and carbidopa. Moreover, it worsened the serotonin behavior syndrome precipitated by 5-HTP and the monoamine oxidase inhibitor tranylcypromine. The serotonin syndrome was also elicited by the combination of milacemide and 5-HTP without tranylcypromine. In vitro, milacemide inhibited both monoamine oxidase A and B from the frontal cortex of rats, to a greater extent for MAO B. This drug is currently under investigation in humans as an antiepileptic agent and precautions for the consequences of monoamine oxidase inhibition should be considered when the drug is used in high doses.
Truong
D D
DD
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, N.Y. 10032.
Diamond
B
B
Pezzoli
G
G
Mena
M A
MA
Fahn
S
S
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D002230:Carbidopa / Q000494:pharmacology; D002540:Cerebral Cortex / Q000201:enzymology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013239:Stereotyped Behavior / Q000187:drug effects*; D014191:Tranylcypromine / Q000494:pharmacology
D000081:Acetamides; D008996:Monoamine Oxidase Inhibitors; C039332:milacemide; D014191:Tranylcypromine; D006916:5-Hydroxytryptophan; D008995:Monoamine Oxidase; D002230:Carbidopa