Effects of monoamine oxidase inhibitors on the acid metabolites of some trace amines and of dopamine in the rat striatum.
The effects of the administration of selective and non-selective inhibitors of monoamine oxidase (MAO) on the concentrations of three trace acid metabolites [phenylacetic acid (PAA); m-hydroxyphenylacetic acid (mHPAA); and p-hydroxyphenylacetic acid (pHPAA)] and of an acid metabolite of dopamine [3,4-dihydroxyphenylacetic acid (DOPAC)] in the rat striatum were determined. Administration of brofaromine (1-100 mg/kg, s.c.) a type AMAO inhibitor, dose-dependently decreased DOPAC and mHPAA levels. pHPAA levels were decreased by 100 mg/kg brofaromine, but PAA levels were unaffected. Doses of deprenyl of less than 100 mg/kg, i.p., had no effect on any of the acids, while 100 mg/kg decreased DOPAC, mHPAA and pHPAA but not PAA levels. Clorgyline, pargyline and tranylcypromine treatment decreased the levels of DOPAC, mHPAA and pHPAA but not PAA. Administration of alpha-monofluoromethyldopa, an inhibitor of aromatic amino acid decarboxylase, decreased the levels of all four acids. It was concluded that deamination of the respective parent amine by type A MAO is primarily responsible for the synthesis of DOPAC and mHPAA, but that another pathway contributes to pHPAA synthesis. It appears that either PAA arises predominantly independently from the actions of MAO or that is removal via transport or further metabolism regulates its concentration.
Dyck
L E
LE
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Durden
D A
DA
Boulton
A A
AA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000588:Amines / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008750:Methyldopa / Q000031:analogs & derivatives / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010648:Phenylacetates / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology
D000588:Amines; D008996:Monoamine Oxidase Inhibitors; D010648:Phenylacetates; D010880:Piperidines; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; C008070:4-hydroxyphenylacetic acid; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; C038213:brofaromine; C005756:2-hydroxyphenylacetic acid; D004298:Dopamine