Plasma 5-hydroxyindoleacetic acid as an indicator of monoamine oxidase-A inhibition in rat brain and peripheral tissues.
We have examined the changes induced by the monoamine oxidase (MAO; EC 1.4.3.4) inhibitors tranylcypromine, clorgyline, and deprenyl on MAO activity and 5-hydroxytryptamine (serotonin, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content in rat brain and blood (plasma and whole blood). The decreases of MAO-A activity observed in the liver and lungs after different doses of clorgyline or tranylcypromine correlated significantly (r > 0.80 in all cases) with the decline of plasma 5-HIAA. This was unaffected by 0.25 and 5 mg kg-1 of deprenyl, indicating that 5-HT was deaminated exclusively in the periphery by MAO-A. It is interesting that very potent and significant correlations (r > 0.75) were found between plasma 5-HIAA and MAO-A activity, 5-HIAA and 5-HT content in brain tissue. These results suggest that plasma 5-HIAA can be used confidently as a peripheral indicator of the inhibition of MAO-A in brain. This may represent a favorable alternative to the analysis of 5-HIAA in CSF in psychiatric patients undergoing antidepressant treatment with nonspecific MAO inhibitors or with the new selective MAO-A inhibitors.
Celada
P
P
Department of Neurochemistry, CSIC, Barcelona, Spain.
Artigas
F
F
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D003010:Clorgyline / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000097:blood* / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D014191:Tranylcypromine / Q000494:pharmacology
D015415:Biomarkers; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D012701:Serotonin; D014191:Tranylcypromine; D006897:Hydroxyindoleacetic Acid; D008995:Monoamine Oxidase; D003010:Clorgyline