Effect of propranolol on monoamine metabolites in cerebrospinal fluid of patients with chronic schizophrenia.

Large doses (960 to 3200 mg/day) of propranolol were taken by eight patients with chronic schizophrenia in a double-blind therapeutic trial. To investigate the effects of such treatment on central monoaminergic processes, samples of cerebrospinal fluid (CSF) were drawn before starting the study and after 31 to 63 days (means = 49 days) on propranolol. Concentrations in CSF of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA), the principal metabolites of norepinephrine, serotonin, and dopamine, were determined by HPLC with electrochemical detection. The level of HVA did not change. CSF 5-HIAA levels decreased an average of 34%, which indicates reduced turnover of serotonin in the central nervous system (CNS). There was a strong correlation between duration of treatment with propranolol and change in CSF 5-HIAA levels. The concentration of MHPG in CSF increased an average of 39%; this could have resulted from increased turnover of CNS norepinephrine as a consequence of the blockade of central beta-adrenoceptors or of altered metabolism and clearance of peripheral MHPG. Psychotic symptoms of the patients, as indicated by the 3-day average score on the Bunney-Hamburg scale, were not affected by treatment.