The glycine-prodrug, milacemide, increases the seizure threshold due to hyperbaric oxygen; prevention by 1-deprenyl.
The novel glycine-prodrug anticonvulsant, milacemide (2-N-pentylaminoacetamide) (500 mg/kg), significantly increased (greater than 400% the seizure threshold induced by hyperbaric oxygen (4.5 atmosphere). This effect was significantly reduced by the selective inhibition of monoamine oxidase B by 1-deprenyl (2.0 mg/kg). 1-Deprenyl alone hardly affected the seizure threshold. These results suggest that, in the brain, milacemide is oxidized to glycine and that this reaction is mediated primarily by monoamine oxidase B. However, the interaction of milacemide metabolites (glycine amide, pentanoate and glycine) as antagonists of receptors of the glutamate NMDA (N-methyl-D-aspartate) subtype cannot be excluded.
D000081:Acetamides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004569:Electroencephalography; D005998:Glycine / Q000494:pharmacology*; D006931:Hyperbaric Oxygenation; D007274:Injections, Intraperitoneal; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D011355:Prodrugs; D051381:Rats; D012640:Seizures / Q000503:physiopathology*; D012642:Selegiline / Q000494:pharmacology*
D000081:Acetamides; D000927:Anticonvulsants; D010627:Phenethylamines; D011355:Prodrugs; C039332:milacemide; D012642:Selegiline; D005998:Glycine