Tolcapona

Tolcapona Uses, Dosage, Side Effects, Food Interaction and all others data.

Tolcapona 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. Tolcapona is associated with a risk of hepatotoxicity.

Tolcapona is a potent, selective, and reversible inhibitor of catechol-O-methyltransferase (COMT). In humans, COMT is distributed throughout various organs. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. COMT is responsible for the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa catalyzing it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery. When tolcapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that these sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease in patients as well as increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa.

Trade Name Tolcapona
Availability Prescription only
Generic Tolcapone
Tolcapone Other Names Tolcapon, Tolcapona, Tolcapone, Tolcaponum
Related Drugs Gocovri, Rytary, Sinemet, Sinemet CR, ropinirole, pramipexole, benztropine, carbidopa / levodopa, Exelon
Type
Formula C14H11NO5
Weight Average: 273.2408
Monoisotopic: 273.063722467
Protein binding

> 99.9% (to serum albumin)

Groups Approved, Withdrawn
Therapeutic Class
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Tolcapona
Tolcapona

Uses

Tolcapona is a catechol-O-methyltransferase (COMT) inhibitor used as adjunct therapy in the symptomatic management of idiopathic Parkinson's disease.

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.

Tolcapona is also used to associated treatment for these conditions: Parkinson's Disease (PD)

How Tolcapona works

The precise mechanism of action of tolcapone is unknown, but it is believed to be related to its ability to inhibit COMT and alter the plasma pharmacokinetics of levodopa, resulting in an increase in plasma levodopa concentrations. The inhibition of COMT also causes a reduction in circulating 3-OMD as a result of decreased peripheral metabolism of levodopa. This may lead to an increase distribution of levodopa into the CNS through the reduction of its competitive substrate, 3-OMD, for transport mechanisms. Sustained levodopa concentrations presumably result in more consistent dopaminergic stimulation, resulting in greater reduction in the manifestations of parkinsonian syndrome.

Toxicity

LD50 = 1600 mg/kg (Orally in rats)

Food Interaction

  • Take with or without food. There is a 10-20% reduction in oral bioavailability when food is given 1 hour before and 2 hours after tolcapone.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Volume of Distribution

  • 9 L

Elimination Route

Rapidly absorbed (absolute bioavailability is about 65%)

Half Life

2-3.5 hours

Clearance

  • 7 L/h

Elimination Route

Tolcapona 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.

Innovators Monograph

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*** Taking medicines without doctor's advice can cause long-term problems.
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