title: Erythrocytes catechol-o-methyl transferase activity is up-regulated after a 3-month treatment by entacapone in parkinsonian patients.
abstract: OBJECTIVE
  Entacapone is a highly potent, reversible, peripherally acting catechol-O-methyl transferase (COMT) inhibitor that is used as an adjunct to L-dopa in the treatment of patients with Parkinson disease (PD). Nevertheless, the consequence of the long-lasting inhibition of COMT by entacapone has never been investigated. We assessed the variation of the soluble red blood cell (S-RBC)-COMT activity after 3 months of chronic treatment by entacapone.
  
  
  METHODS
  Twelve consecutive white PD patients (3 women and 9 men; mean age, 65.7 ± 2.4 years) with L-dopa-related motor fluctuations were assessed. Entacapone 200 mg was given in combination with each scheduled L-dopa/dopa decarboxylase inhibitor dose (range, 3-5 doses daily). The S-RBC-COMT activity was determined both before entacapone administration (baseline) and twice, respectively, after 1 and 3 months treatment with entacapone, that is, on morning, after at least a 12-hour withdrawal of entacapone and L-dopa and before the following first daily administration.
  
  
  RESULTS
  Mean baseline S-RBC-COMT activity was 0.72 ± 0.09 pmol/min per milligram (range, 0.30-1.29 pmol/min per milligram) of protein. After 3 months, the level increased significantly in all PD patients from 0.72 ± 0.09 pmol/min per milligram (range, 0.30-1.29 pmol/min per milligram) to 1.19 ± 0.13 pmol/min per milligram (range, 0.58-2.14 pmol/min per milligram) of protein (P < 0.01), which corresponds to a mean increase of 72.9 ± 9.2% (range, 24%-146%).
  
  
  CONCLUSIONS
  Our findings suggest that a long-lasting inhibition of the COMT may limit the efficacy of entacapone by development of a tolerance. Moreover, one may assume that an abrupt withdrawal of the treatment will be followed by a dramatic worsening of motor disability.
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France. david.maltete@chu-rouen.fr
authors.forename: David
authors.initials: D
authors.lastname: Maltête
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Cottard
authors.forename: Bruno
authors.initials: B
authors.lastname: Mihout
authors.forename: Jean
authors.initials: J
authors.lastname: Costentin
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002394:Catechol O-Methyltransferase / Q000097:blood*; D002396:Catechols / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000978:Antiparkinson Agents; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; C071192:entacapone; D002394:Catechol O-Methyltransferase