Effects of monoamine oxidase inhibitors on levels of catechols and homovanillic acid in striatum and plasma.
Levels of homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and dihydroxyphenylglycol (DHPG) in plasma and the striatium were measured after inhibition of monoamine oxidase type A (MAO-A) by clorgyline (4 mg/kg i.p.), MAO-B by (-)deprenyl (1 mg/kg i.p.), both MAO-A and MAO-B by nialamide (75 mg/kg i.p.) or peripheral neuronal MAO by debrisoquin (40 mg/kg i.p.). Levels of HVA in plasma decreased by about 60% after single doses of nialamide or clorgyline, by about 80% after repeated doses of nialamide, by about 40% after a single dose of debrisoquin and by about 50% after repeated doses of debrisoquin. The administration of clorgyline, nialamide or debrisoquin significantly decreased concentrations of DOPAC and DHPG in plasma, whereas (-)deprenyl did not affect levels of DHPG or HVA. None of the MAO inhibitors produced more than about 80% depression of levels of any of the deaminated metabolites. The results suggest that most of the HVA in plasma is derived from deamination of DA by MAO-A in peripheral neurons; that DOPAC in plasma is derived from cells outside the central nervous system; that DHPG in plasma is derived virtually exclusively from the metabolism of norepinephrine in sympathetic nerve endings and that residual levels of HVA after treatment with debrisoquin provide an improved but limited indication of central dopaminergic activity.
Hovevey-Sion
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Intramural Research Program, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
Kopin
I J
IJ
Stull
R W
RW
Goldstein
D S
DS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood / Q000378:metabolism; D000818:Animals; D002396:Catechols / Q000097:blood / Q000378:metabolism*; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003647:Debrisoquin / Q000494:pharmacology; D006719:Homovanillic Acid / Q000097:blood / Q000378:metabolism*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009526:Nialamide / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology
D002396:Catechols; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D008734:Methoxyhydroxyphenylglycol; D003010:Clorgyline; D009526:Nialamide; C010117:3,4-dihydroxyphenylglycol; D003647:Debrisoquin; D009638:Norepinephrine; D006719:Homovanillic Acid