NOREPINEPHRINE METABOLISM IN THE CENTRAL NERVOUS SYSTEM OF MAN: STUDIES USING 3‐METHOXY‐4‐HYDROXYPHENYLETHYLENE GLYCOL LEVELS IN CEREBROSPINAL FLUID

Abstract

Abstract —Levels of 3‐methoxy‐4‐hydroxyphenylethylene glycol (MHPG), a major metabolite of norepinephrine, were measured in human CSF by gas‐liquid chromatography. MHPG concentrations were similar in both ventricular and lumbar CSF samples; about 30 per cent of the MHPG from either source occurred as the sulphate conjugate. There was relatively little entry of intravenously infused [ 14 C]MHPG into lumbar spinal fluid. Both α‐methylparatyrosine, an inhibitor of tyrosine hydroxylase, and fusaric acid, an inhibitor of dopamine‐β‐hydroxylase, significantly diminished MHPG values. On the other hand, doses of l ‐DOPA or probenecid, sufficient to substantially elevate CSF levels of the dopamine metabolite, homovanillic acid, failed to alter the spinal fluid content of MHPG. CSF concentrations of MHPG in patients with Parkinson's disease or the other central nervous system disorders studied did not differ significantly from control levels. The results suggest that MHPG values in CSF may provide an index to norepinephrine metabolism in the central nervous system of man.