Effect of probenecid on free 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and its sulphate in human cerebrospinal fluid

In a mixed group of 46 patients with affective disorder, or with various neurologic disorders, high doses of probenecid (100 mg/kg over 18 hr) produced a significant increase in lumbar cerebrospinal fluid (CSF) levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the major metabolite of norepinephrine centrally. This increase (averaging 60%) is modest in comparison to probenecid induced increases in homovanillic acid (HVA) or 5-hydroxyindo-leacetic acid (5-HIAA). Analysis for free MHPG and its sulfate showed no significant differences for either compound after nine hours. After 18 hours of treatment significant increases in free MHPG and small but not significant increases of MHPG.SO₄ were found. These results suggest that a probenecid sensitive active transport mechanism for MHPG.SO₄ of the degree demon-strated for HVA and 5-HIAA in humans, and for MHPG.SO₄ in rats, does not occur in human CSF.