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Catechol-O-methyltransferase inhibitors

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

  • COMT is one of the enzymes that catabolise dopamine - both within and outside the nervous system
  • COMT inhibitors therefore increase the bioavailability of dopamine (both extra and intracerebrally)
  • COMT inhibitors can reverse wearing-off effects of L-dopa without the need for an increase in daily dose
  • a common consequence of initiation of COMT inhibitor therapy is an exacerbation of L-dopa induced side effects e.g. dyskinesias; these should settle when the L-dopa dose has been appropriately adjusted
  • other side effects of COMT inhibitors include:
    • diarrhoea - often self-limiting - occurs in approximately 10% of patients on standard dose
    • may be some orange discoloration of patient's urine

NICE guidance states (1):

  • COMT inhibitors may be used to reduce motor fluctuations in people with later Parkinson's disease (PD)
  • in view of problems with reduced concordance, people with later PD taking entacapone should be offered a triple combination preparation of levodopa, carbidopa and entacapone
  • tolcapone should only be used after entacapone has failed in people with later PD due to lack of efficacy or side effects. Liver function tests are required every 2 weeks during the first year of therapy, and thereafter in accordance with the 'Summary of product characteristics'


  1. NICE (June 2006). Parkinson's disease

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