Assessment of brain dopamine metabolism from plasma HVA and MHPG during debrisoquin treatment: validation in monkeys treated with MPTP.
Homovanillic acid (HVA) is formed from dopamine that escapes conversion to norepinephrine in noradrenergic neurons throughout the body as well as from dopamine synthesized in dopaminergic neurons that are mainly in brain. Debrisoquin has been used to diminish peripheral formation of dopamine to enhance the value of plasma HVA as an index of brain dopaminergic activity. This enhancement may be improved if the residual HVA formed in noradrenergic neurons could be estimated. By use of simultaneously measured plasma levels of the major metabolite of norepinephrine, the degree of residual catecholamine formation in noradrenergic neurons can be estimated. By extrapolating to zero MHPG levels the linear relationship of plasma HVA to plasma MHPG, an estimate of HVA formed solely from brain dopaminergic neurons can be obtained. This method was tested by administering debrisoquin to monkeys before and after destruction of brain dopaminergic neurons with MPTP. After MPTP treatment there were decreases in plasma HVA that were relatively greatest when considered in relation to MHPG. The results support the view that the plasma HVA levels at extrapolated zero MHPG levels improves precision in assessing brain dopamine metabolism.
Kopin
I J
IJ
National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
Bankiewicz
K S
KS
Harvey-White
J
J
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003647:Debrisoquin / Q000494:pharmacology*; D015198:Designer Drugs / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006018:Glycols / Q000097:blood*; D006719:Homovanillic Acid / Q000097:blood* / Q000134:cerebrospinal fluid; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D008253:Macaca mulatta; D008734:Methoxyhydroxyphenylglycol / Q000097:blood* / Q000134:cerebrospinal fluid; D011725:Pyridines / Q000494:pharmacology*
D015198:Designer Drugs; D006018:Glycols; D007546:Isoquinolines; D011725:Pyridines; D008734:Methoxyhydroxyphenylglycol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D003647:Debrisoquin; D006719:Homovanillic Acid