title: 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.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Scheinin
authors.forename: S
authors.initials: S
authors.lastname: Karhuvaara
authors.forename: P
authors.initials: P
authors.lastname: Ojala-Karlsson
authors.forename: A
authors.initials: A
authors.lastname: Kallio
authors.forename: M
authors.initials: M
authors.lastname: Koulu
mesh_terms: D000328:Adult; D001549:Benzamides / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D004837:Epinephrine / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D020926:Medetomidine; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000097:blood*; D020912:Moclobemide; D009638:Norepinephrine / Q000097:blood; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
chemical_list: D001549:Benzamides; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; C050701:atipamezole; D008734:Methoxyhydroxyphenylglycol; D020926:Medetomidine; D020912:Moclobemide; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D004837:Epinephrine