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Dopamine Metabolism and Disposition in Schizophrenic PatientsStudies Using Debrisoquin
James W. Maas, MD;
Salvador A. Contreras, MD;
Ermias Seleshi, MD;
Charles L. Bowden, MD
Arch Gen Psychiatry. 1988;45(6):553-559.
Abstract
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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.
Author Affiliations
From the Department of Psychiatry, The University of Texas Health Science Center at San Antonio (Drs Maas, Seleshi, and Bowden), and Audie L. Murphy Memorial Veterans' Hospital, San Antonio (Dr Contreras).
Footnotes
Accepted for publication Nov 17, 1987.
Reprint requests to Department of Psychiatry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78284-7792 (Dr Maas).
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