Plasma debrisoquin levels in the assessment of reduction of plasma homovanillic acid. The debrisoquin method.
Plasma concentrations of unconjugated homovanillic acid (pHVA) reflect both central nervous system (CNS) and peripheral dopamine metabolism. Debrisoquin sulfate (DBQ) blocks peripheral, but not CNS, production of HVA from dopamine. Administration of DBQ has been used to decrease the proportion of peripherally produced HVA in pHVA measurements, making such measurements more reflective of CNS turnover of dopamine. We studied the relationships between DBQ dose, plasma DBQ (pDBQ) levels, and changes in pHVA in a group of 21 subjects (9 normal controls and 12 with Tourette's syndrome). DBQ dose was moderately correlated with pDBQ levels (r = 0.63, p = 0.002). Subjects (n = 8) with mean pDBQ levels above 60 ng/ml had a 48% to 66% decrease in mean pHVA levels; this may reflect nearly complete inhibition of peripheral HVA production. Subjects (n = 13) with mean pDBQ levels below 55 ng/ml had decreases in pHVA levels from 10% to 58%. No debrisoquin was detected in cerebrospinal fluid samples. These data suggest that pDBQ levels above 60 ng/ml are sufficient to assure substantial inhibition of peripheral HVA production and that monitoring pDBQ levels may be useful when employing this method for studying CNS metabolism.
Riddle
M A
MA
Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06510-8009.
Jatlow
P I
PI
Anderson
G M
GM
Cho
S C
SC
Hardin
M T
MT
Cohen
D J
DJ
Leckman
J F
JF
D000328:Adult; D003647:Debrisoquin / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006719:Homovanillic Acid / Q000097:blood*; D006801:Humans; D007546:Isoquinolines / Q000097:blood*; D008297:Male; D008722:Methods; D005879:Tourette Syndrome / Q000097:blood
D007546:Isoquinolines; D003647:Debrisoquin; D006719:Homovanillic Acid