Differential inhibition of neuronal and extraneuronal monoamine oxidase.
This study examined whether the neuronal and extraneuronal sites of action of two monoamine oxidase (MAO) inhibitors, l-deprenyl and debrisoquin, could be distinguished by their effects on plasma concentrations of catecholamine metabolites. Plasma concentrations of the intraneuronal deaminated metabolite of norepinephrine, dihydroxyphenylglycol (DHPG), were decreased by 77% after debrisoquin and by 64% after l-deprenyl administration. Plasma concentrations of the extraneuronal O-methylated metabolite of norepinephrine, normetanephrine, were increased substantially more during treatment with l-deprenyl than with debrisoquin (255% compared to a 27% increase). The comparable decreases in plasma concentrations of DHPG indicate a similar inhibition of intraneuronal MAO by both drugs. Much larger increases in normetanephrine after l-deprenyl than after debrisoquin are consistent with a site of action of the latter drug directed at the neuronal rather than the extraneuronal compartment. Thus, differential changes in deaminated and O-methylated amine metabolites allows identification of neuronal and extraneuronal sites of action of MAO inhibitors.
Eisenhofer
G
G
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1424, USA.
Lenders
J W
JW
Harvey-White
J
J
Ernst
M
M
Zametkin
A
A
Murphy
D L
DL
Kopin
I J
IJ
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002395:Catecholamines / Q000378:metabolism; D003647:Debrisoquin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology*; D009638:Norepinephrine / Q000378:metabolism
D002395:Catecholamines; D008995:Monoamine Oxidase; D003647:Debrisoquin; D009638:Norepinephrine