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More about Tolcapone

What is/are Tolcapone?

Tolcapone (tradename Tasmar) is a selective, potent and reversible nitro catechol type inhibitor of enzyme catechol-O-methyl transferase (COMT).

Medical uses

Tolcapone is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa medication that is conventionally paired with an aromatic L-amino acid decarboxylase (AADC) inhibitor.

Normally, administration of levodopa is compromised when COMT converts it to 3-methoxy-dopa. By preventing this effect, more of the levodopa that is administered reaches the CNS. Additionally, levodopa that is in the CNS, after being converted to dopamine, will not be degraded by COMT when tolcapone inhibits COMT activity.

Adverse effects

Tolcapone has demonstrated significant hepatotoxicity that limits the drug's utility. Entacapone, another COMT inhibitor, is an alternative selection for L-DOPA adjunct therapy in the treatment of Parkinson's disease, largely since it has a more favorable toxicity profile.

This hepatoxicity can be attributed to elevated levels of transminases, but studies have shown that minimal risk exists for those without preexisting liver conditions when their enzyme levels were being monitored. No clear mechanism is implicated in Tolcapone induced liver toxicity, but it has been hypothesized that it has something to do with abnormal mitochondrial respiration due to the uncoupling of oxidative phosphorylation.

Other side effects that result from the administration of Tolcapone regard the increase in dopaminergic activity, digestive symptoms and liver function. Treatment with Tolcapone runs the risk of eliciting or prolonging dyskinesia, this can be counteracted by decreasing the dose of L-DOPA.This occurs because the administration of Tolcapone results in the accumulation of the biological methyl donor S-adenosyl-L-methionine (SAM) in the striatum that works to induce symptoms of PD.

Digestive symptoms include nausea, diarrhea, orthostatic hypotension, urine discoloration and dizziness. Tolcapone causes more severe diarrhea than entacapone.

This article uses material from the Wikipedia article Tolcapone, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

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