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Membrane‐bound COMT inhibition by Nebicapone
Author(s) -
Bonifacio Maria Joao,
Torrão Leonel,
Wright Lyndon,
SoaresdaSilva Patricio
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1013-a
Subject(s) - ackermann function , enzyme , in vivo , catechol o methyl transferase , chemistry , aromatic l amino acid decarboxylase , in vitro , enzyme inhibition , membrane , catechol , ex vivo , enzyme assay , enzyme inhibitor , biochemistry , pharmacology , medicine , biology , genotype , inverse , geometry , mathematics , microbiology and biotechnology , gene
Nebicapone is a new nitrocatechol‐type inhibitor of Catechol‐O‐methyltransferase, developed for the treatment of Parkinson’s Disease as an adjunct to the l‐dopa/aromatic amino acid decarboxylase inhibitor therapy. The interaction of this compound with the soluble form of the enzyme has been described, however no information has been reported concerning the interaction with the membrane‐bound form of the enzyme. In this study, we have compared the inhibition of S‐ and MB‐COMT in vitro by determining the inhibition constants from Ackermann‐Potter analyses. The inhibition of both forms of the enzyme in vitro ex‐vivo was assessed in livers collected from rats administered orally with several doses of nebicapone. The molar equivalency values determined from the Ackermann‐Potter analysis were used to normalize the enzyme concentrations in these studies. Nebicapone appears to have a higher sensitivity for MB‐COMT inhibition than S‐COMT as translated by a lower Ki (0.03±0.01 versus 0.13±0.07). In vivo, however, nebicapone inhibits both forms of the enzyme to the same extent, when an equimolar amount of enzyme is considered.