Cerebrospinal fluid (CSF; n = 5) and plasma (n = 7) levels of
norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (
MHPG) were examined in abstinent normotensive men with
alcohol amnestic disorder during placebo and after 2 wk of
clonidine treatment (6 or 12 micrograms/kg/day).
Clonidine reduced concentrations of NE and both free and total
MHPG in CSF and plasma. The CNS contribution to CSF free
MHPG also decreased (as estimated from the differential reductions in CSF and plasma levels). Percent reductions in CSF and plasma NE were substantially greater than those for
MHPG, suggesting diminished CNS and peripheral NE release and turnover. CSF levels of
homovanillic acid (HVA), which is derived solely from CNS
dopamine metabolism, rose in each patient, whereas the CSF
serotonin metabolite, 5-hydroxyindoleacetic
acid, did not change. Thus the increase in HVA cannot be attributed to inhibition of
acid transport from brain to blood. Changes in central noradrenergic and dopaminergic activity correlated inversely; thus diminished NE release and enhanced
dopamine metabolism may both contribute to the effects of
clonidine in man.