title: COMT inhibition by entacapone does not affect growth hormone or prolactin secretion in healthy volunteers.
abstract: We studied the effects of entacapone, a novel inhibitor of the enzyme catechol-O-methyltransferase (COMT), on spontaneous and levodopa (LD) modulated secretion of growth hormone (GH) and prolactin (PRL) in 12 healthy male volunteers. The study had a double-blind, cross-over design with two experimental settings. In the first setting the subjects received a single oral dose of 400 mg of entacapone or matching placebo in a randomized order. In the second setting, a single oral dose of 300 mg of LD and 75 mg of carbidopa was administered concomitantly with either 400 mg of entacapone or matching placebo in a randomized order. Entacapone had no effect on resting levels of GH, but PRL concentrations in plasma were slightly lower after entacapone than after placebo. As expected, LD/carbidopa increased the concentration of GH and decreased that of PRL. The effects of LD were not influenced by concomitant administration of entacapone. Compared with the administration of LD/carbidopa together with placebo, concomitant administration of entacapone increased the AUC of LD by 29% and reduced the AUC of 3-O-methyldopa (a metabolite of LD produced by COMT) by 69%. Entacapone appears not to enhance the effects of LD on hypothalamic-pituitary function, although the LD dose used may have been bigger than optimal for detection of a small modulatory influence.
authors.affiliation: Orion Research Center, Orion-Farmos, Espoo, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Keränen
authors.forename: A
authors.initials: A
authors.lastname: Gordin
authors.forename: M
authors.initials: M
authors.lastname: Koulu
authors.forename: M
authors.initials: M
authors.lastname: Scheinin
authors.forename: S
authors.initials: S
authors.lastname: Antila
authors.forename: S
authors.initials: S
authors.lastname: Sundberg
authors.forename: T
authors.initials: T
authors.lastname: Wikberg
mesh_terms: D000328:Adult; D000978:Antiparkinson Agents / Q000097:blood / Q000493:pharmacokinetics; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D018592:Cross-Over Studies; D004298:Dopamine / Q000502:physiology; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D009570:Nitriles; D010919:Placebos; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000097:blood
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D010919:Placebos; D019382:Human Growth Hormone; D014443:Tyrosine; D007980:Levodopa; C071192:entacapone; D011388:Prolactin; C008404:3-methoxytyrosine; D004298:Dopamine