title: Inhibition of human erythrocyte and gastroduodenal catechol-O-methyltransferase activity by nitecapone.
abstract: The effect of increasing single oral doses of the novel catechol-O-methyltransferase (COMT) inhibitor, nitecapone, on enzyme activity in red cells (RBC) and gastroduodenal COMT activity has been studied in healthy male volunteers. A dose-dependent decrease in RBC COMT activity was seen in all cases after 1 to 150 mg of the drug. The highest dose of 300 mg did not produce much more inhibition of COMT than 150 mg. The inhibition was not complete; at the highest doses the COMT activity was reduced by 50-60%. The effect and the duration of the inhibition in RBC COMT was strongly correlated with plasma nitecapone concentrations in the dose range up to 150 mg. RBC COMT activity recovered fully in 4 h after medication. Gastric mucosal COMT activity was several-fold higher than that in RBCs. It was also dose-dependently inhibited at the two doses (25 and 100 mg) studied. The inhibition of gastric and duodenal COMT was greater than that in RBCs. This also indicates that nitecapone is locally active in the gastroduodenal tract. The results confirm nitecapone as a potent COMT inhibitor in human tissues. New COMT inhibitors may provide a valuable approach to the treatment of Parkinson's disease in combination with L-dopa and dopa decarboxylase inhibitor therapy.
authors.affiliation: Research Centre, Orion Pharmaceutica, Helsinki, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Schultz
authors.forename: S
authors.initials: S
authors.lastname: Tarpila
authors.forename: A C
authors.initials: AC
authors.lastname: Bäckström
authors.forename: A
authors.initials: A
authors.lastname: Gordin
authors.forename: E
authors.initials: E
authors.lastname: Nissinen
authors.forename: P
authors.initials: P
authors.lastname: Pohto
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D002394:Catechol O-Methyltransferase / Q000032:analysis / Q000097:blood / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D005773:Gastroscopy; D006801:Humans; D008297:Male; D010422:Pentanones / Q000378:metabolism / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000187:drug effects / Q000201:enzymology; D013270:Stomach / Q000187:drug effects / Q000201:enzymology*
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D010422:Pentanones; C057364:nitecapone; D002394:Catechol O-Methyltransferase