COMT (Catecholamine O-Methyl Transferase) inhibitors for the management of Parkinson’s Disease

The emergence of Entacapone (Contan) and Tolacone (Tasmar) is important because they prevent the peripheral catabolism of L-dopa to inactive metabolites, thus enhancing the actions of L-dopa and its product dopamine, incidentally reducing the dose requirement. These drugs are in use more and more, the consequences are not exactly known, but we are theoretically worried about enhancement of epinephrine effects for pts taking COMT inhibitors.



Entacapone (Contan) is only used for pts taking L-dopa/carbidopa; it is an adjunct. It is used in pts where levodopa therapy is wearing off. Contan decreases the metabolism of levodopa before reaching the brain and prolongs the actions of levodopa/carbidopa. Side effects of Contan include: dsykinesia, nausea, diarrhea, abdominal pain, urine discoloration. Contan is not used as monotherapy for Parkinson’s disease.



Requip (ropinirole) was the first D3 receptor agonist. It isn’t popular among neurologists. Mirapex (pramipexole) is also a D3 receptor agonist. With this drug, pt may fall asleep abruptly, have hallucinations, become demented, and have orthostatic hypotension, so there’s a lot to worry about. D3 receptors might be in the basal ganglion and control movement disorders, but they’re also stimulating the D3 receptor elsewhere where behavior and cognitive function is occurring.

Category: Pharmacology Notes