2793 Tolcapone Tolcapone is a drug that inhibits the enzyme catechol-O-methyl transferase (COMT). It is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa medication. It is a yellow, odorless, non-hygroscopic, crystalline compound. Tolcapone is associated with a risk of hepatotoxicity. 134308-13-7 4659569 C14H11NO5 273.063720 White powder. 5.69e-02 g/L Oral, rapidly absorbed (absolute bioavailability is about 65%) Tolcapone 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. Dyskinesia 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 Parkinson's disease. (Wikipedia) The main metabolic pathway of tolcapone is glucuronidation. Route of Elimination: Tolcapone is almost completely metabolized prior to excretion, with only a very small amount (0.5% of dose) found unchanged in urine. The glucuronide conjugate of tolcapone is mainly excreted in the urine but is also excreted in the bile. Half Life: 2-3.5 hours LD50: 1600 mg/kg (Oral, Rats) (A308) No indication of carcinogenicity to humans (not listed by IARC). Used as an adjunct to levodopa/carbidopa therapy for the symptomatic treatment of Parkinson's Disease. This drug is generally reserved for patients with parkinsonian syndrome receiving levodopa/carbidopa who are experiencing symptom fluctuations and are not responding adequately to or are not candidates for other adjunctive therapies. Tolcapone has demonstrated significant hepatotoxicity that limits the drug's utility. 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. (Wikipedia) Digestive symptoms include nausea, diarrhea, orthostatic hypotension, urine discoloration and dizziness. Tolcapone causes more severe diarrhea than entacapone. (Wikipedia) Hospitalization is advised. General supportive care is indicated. (L1712) Tolcapone-induced dyskinesia can be counteracted by decreasing the dose of L-DOPA (Wikipedia). 2009-07-21T20:26:36Z 2026-03-27T01:33:11Z Tolcapone C07949 63630 CPD-7664 Tolcapone DB00323 TCW true CC1=CC=C(C=C1)C(=O)C1=CC(=C(O)C(O)=C1)[N+]([O-])=O C14H11NO5 InChI=1S/C14H11NO5/c1-8-2-4-9(5-3-8)13(17)10-6-11(15(19)20)14(18)12(16)7-10/h2-7,16,18H,1H3 MIQPIUSUKVNLNT-UHFFFAOYSA-N 273.2408 273.063722467 Exogenous Solid 4 HMDB14468 CHEMBL1324 3848682 CHEM002170 DTXSID3023685 NS00007380 5-(4-methylbenzoyl)-3-nitrobenzene-1,2-diol