Catechol-O-methyltransferase inhibitors

• 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'

Reference:

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