Dopamine metabolism and disposition in schizophrenic patients. Studies using debrisoquin
J. W. Maas, S. A. Contreras, E. Seleshi and C. L. Bowden
Department of Psychiatry, University of Texas Health Science Center, San Antonio 78284-7792.
Debrisoquin sulfate, a monoamine oxidase inhibitor that does not enter the
brain, was administered to 23 schizophrenic subjects. Plasma, cerebrospinal
fluid (CSF), and urine samples were obtained before and during debrisoquin
administration and were assayed for their content of norepinephrine and
dopamine metabolites, ie, 3-methoxy-4-hydroxyphenylglycol (MHPG),
homovanillic acid (HVA), and dihydroxyphenylacetic acid. The severity of
the patient's schizophrenic symptoms was also assessed with several types
of rating scales. During debrisoquin administration there were significant
reductions in plasma, urine, and CSF MHPG levels. Regression analyses
suggested that the reduction in CSF MHPG level was probably due to the
reduction in plasma MHPG level, which contributes to the CSF MHPG pool.
Debrisoquin administration was not associated with changes in CSF HVA
level, although it did produce marked reductions in plasma and urinary HVA
and dihydroxyphenylacetic acid levels. Significant correlations between
plasma and CSF concentrations of HVA were noted during, but not before,
debrisoquin administration. Before debrisoquin administration there were
trends toward positive relationships between symptom severity and plasma
HVA concentrations, which became stronger and statistically significant
during debrisoquin administration. These data suggest that debrisoquin may
be used as a research tool to create a condition in which measures of HVA
in peripheral body fluids reflect dopamine system function and metabolism
within the central nervous system.
