Relative Importance of 3‐Methoxy‐4‐Hydroxyphenylglycol and 3,4‐Dihydroxyphenylglycol as Norepinephrine Metabolites in Rat, Monkey, and Humans

Abstract

A gas chromatographic-mass spectrometric assay, which allowed simultaneous measurement of 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG), was used to show that the concentration of MHPG in primate CNS far exceeded that of DHPG and that both metabolites were mainly in the unconjugated form. In rat brain, DHPG concentration was generally higher than that of MHPG, and both existed predominantly as conjugates. Rat and primate plasma contained more MHPG than DHPG. In plasma of primates but not of rats, higher proportions of the metabolites were conjugated, compared to those in brain. Significant correlations existed between MHPG and DHPG in rat brain, monkey brain, human plasma, and both monkey CSF and plasma. In monkeys, a significant CSF-plasma correlation was found for MHPG, but not for DHPG. Acute administration of piperoxane raised rat brain MHPG and DHPG concentration; desipramine prevented this rise in DHPG, but not in MHPG. Desipramine alone decreased DHPG, but not MHPG, concentration. Piperoxane increased monkey brain MHPG, but not DHPG, concentration. These data suggest that DHPG is a valuable metabolite to measure when assessing norepinephrine metabolism in the rat. Under certain conditions, measurement of rat brain MHPG and DHPG may provide information concerning the site of norepinephrine metabolism. However, in primates the importance of monitoring DHPG, in addition to MHPG, is uncertain.