Simultaneous delivery of valproic acid and glycine to the brain. Deamination of 2-propylpentylglycinamide by monoamine oxidase B.
2-Propylpentylglycinamide (2-PPG), a branched aliphatic amine derivative, was found to be readily deaminated by rat liver monoamine oxidase B in vitro and in vivo. The deamination leads to production of 2-propyl-1-pentaldehyde, which can be subsequently converted to valproic acid (VPA), and glycinamide, which is then subsequently converted to glycine. Absorption and biotransformation of a single ip dose of 2-PPG into blood as well as transfer of the drug and its metabolite into the brain were rapid processes. Although VPA (an anticonvulsant) and glycine (an inhibitory neurotransmitter) can be detected in the brain following administration of 2-PPG, its anticonvulsant action cannot be determined. 2-PPG at relatively low doses exhibited distinct tremor effects. Furthermore, 2-PPG appeared to potentiate the convulsant effect induced by pentylenetetrazol.
Yu
P H
PH
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Davis
B A
BA
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003641:Deamination; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D011355:Prodrugs / Q000378:metabolism*; D051381:Rats; D014202:Tremor / Q000139:chemically induced; D014635:Valproic Acid / Q000378:metabolism*
D008996:Monoamine Oxidase Inhibitors; D011355:Prodrugs; C068588:N-(2-propylpentyl)glycinamide; D014635:Valproic Acid; D008995:Monoamine Oxidase; D005998:Glycine