Tolcapone

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Cat Number

API0232242

CAS Number

134308-13-7

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CAS Number

134308-13-7

EINECS

694-343-9

Storage

Store at 2-8°C

Synonyms

Tasmar; 3,4-Dihydroxy-4'-methyl-5-nitrobenzophenone; Ro 40-7592; (3,4-Dihydroxy-5-nitrophenyl)(4-methylphenyl)methanone

Molecular Formula

C14H11NO5

Molecular Weight

273.24

Smiles

CC1=CC=C(C=C1)C(=O)C2=CC(=C(C(=C2)O)O)[N+](=O)[O-]

Appearance

Yellow solid

Melting Point

126-128°C

Boiling Point

485.6±45.0°C at 760 mmHg (Predicted)

Relative Density

1.419±0.06 (Predicted)

General Description

Tolcapone is a synthetic nitrocatechol derivative with a methyl group, belonging to the class of catechol-O-methyltransferase (COMT) inhibitors. Its chemical structure is 3,4-dihydroxy-5-(4-methylbenzoyl)-2-nitrophenyl]acetic acid. Tolcapone is a white to off-white crystalline powder, practically insoluble in water but soluble in organic solvents.

Mechanism of Action

Tolcapone inhibits the enzyme catechol-O-methyltransferase (COMT), which is responsible for the metabolism of levodopa and dopamine. By blocking the methylation of levodopa, it increases the availability of levodopa in the brain, enhancing its efficacy in the treatment of Parkinson's disease.

Application

Tolcapone is indicated as an adjunct to levodopa and carbidopa for the treatment of Parkinson's disease in patients who are experiencing fluctuations in motor response (on-off phenomena). It is effective in reducing the "off" time and improving motor function.

Tolcapone, a COMT inhibitor used in Parkinson’s disease, reduced viability of neuroblastoma cell lines (including primary cells) in a dose‑dependent manner, inducing caspase‑3‑mediated apoptosis, increasing ROS, and decreasing ATP per cell. COMT siRNA phenocopied these effects. In xenograft models, tolcapone inhibited tumor growth and reduced time‑to‑event. Tolcapone is cytotoxic to neuroblastoma and warrants further investigation as a novel therapy.

Fig. 1 Tolcapone exhibits cytotoxicity as a single agent in four NB cell lines and two primary tumors. (Maser T, et al., 2017)

References

Maser T, et al. Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma. Cancer Med. 2017;6(6):1341-1352.

In a double-blind crossover trial of 55 non-treatment-seeking individuals with alcohol use disorder, tolcapone (100 mg TID for 5 days) significantly reduced self-reported alcohol consumption (p=0.045), with the reduction correlated with decreased impulsive decision-making (r=0.40, p=0.0053). Laboratory bar consumption was not affected. Adverse events were low and similar to placebo. COMT inhibitors like tolcapone may be useful therapeutics for AUD.

Fig. 2 Impulsive Choice. (Coker AR, et al., 2020)

References

Coker AR, et al. The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder. Psychopharmacology (Berl). 2020;237(10):3139-3148.

Does Tolcapone require protection from light and oxygen during storage?

Yes, it is highly sensitive to light and oxygen. The nitrocatechol moiety is prone to oxidation and photodegradation. Store in airtight, light-resistant containers under inert gas (nitrogen) at 2-8°C.

What is the recommended storage temperature for Tolcapone?

Store at 2-8°C (refrigerated). At room temperature, rapid oxidation to the corresponding quinone occurs, reducing therapeutic activity.

Is Tolcapone stable in tablet formulations with standard excipients?

Yes, when formulated with antioxidants (e.g., ascorbic acid) and moisture-protective packaging.

How is the impurity tolcapone quinone (an oxidative degradation product) monitored?

This primary degradation product is specifically quantified using a stability-indicating HPLC method with electrochemical detection, ensuring it remains within ICH limits.