Plasma 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are insensitive indicators of alpha 2-adrenoceptor mediated regulation of norepinephrine release in healthy human volunteers

Life Sci. 1991;49(1):75-84. doi: 10.1016/0024-3205(91)90581-u.


The usefulness of the plasma concentrations of two major metabolites of norepinephrine (NE), 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG), as indicators of neuronal NE release was investigated. The potent alpha 2-adrenoceptor agonist, dexmedetomidine, induced only about 15% maximal reductions in the metabolite concentrations, in spite of almost total inhibition of neuronal NE release, as evidenced by 90% reductions in plasma NE concentrations. Similarly, administration of the alpha 2-adrenoceptor antagonist atipamezole was followed by only small increases in plasma DHPG and no change in MHPG levels, in spite of almost six-fold, albeit short-lasting, increases in plasma NE. In contrast, a single dose of the reversible monoamine oxidase type A (MAO-A) inhibitor moclobemide reduced plasma DHPG levels by 78% and MHPG levels by 51%. It is concluded that the plasma concentrations of DHPG and MHPG are largely determined by intraneuronal, MAO-A-dependent metabolism of NE, and do not accurately reflect acute alterations in neuronal NE release. The concentration of NE in venous plasma is clearly a more sensitive indicator of alpha 2-adrenoceptor-mediated regulation of NE release.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Benzamides / pharmacology
  • Chromatography, High Pressure Liquid
  • Electrochemistry
  • Epinephrine / metabolism*
  • Humans
  • Imidazoles / pharmacology
  • Male
  • Medetomidine
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / blood*
  • Moclobemide
  • Norepinephrine / blood
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / metabolism*
  • Reference Values


  • Benzamides
  • Imidazoles
  • Receptors, Adrenergic, alpha
  • atipamezole
  • Methoxyhydroxyphenylglycol
  • Medetomidine
  • Moclobemide
  • 3,4-dihydroxyphenylglycol
  • Norepinephrine
  • Epinephrine