This study presents an electroanalytical approach to measure the catechol-O-methyltransferase (COMT) inhibitor tolcapone (TOL) using a boron-doped diamond (BDD) electrode. The application of cyclic voltammetry (CV) technique revealed that TOL exhibited a distinct, diffusion-controlled, irreversible anodic peak at a potential of approximately +0.71 V (vs. Ag/AgCl) in a 0.1 mol L phosphate buffer solution (PBS) with a pH of 2.5. The oxidation of TOL is highly dependent on the pH and supporting electrolytes. Based on the data obtained from the pH investigation, a proposed mechanism for the electro-oxidation of TOL is suggested. Using the square wave voltammetry (SWV) technique, a satisfactory linear relationship was observed at approximately +0.66 V in a 0.1 mol L PBS with a pH of 2.5. The presented method exhibited linearity within the concentration range between 1.0-50.0 μg mL (3.7 × 10-1.8 × 10 mol L), with a limit of detection (LOD) of 0.29 μg mL (1.1 × 10 mol L). The BDD electrode demonstrated good selectivity against inorganic ions and filler materials interference. Finally, the suitability of the developed approach was assessed by measuring TOL in tablet formulations, resulting in favorable recoveries ranging from 103.4% to 106.2%.
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http://dx.doi.org/10.55730/1300-0527.3650 | DOI Listing |
Expert Opin Drug Metab Toxicol
November 2024
Department of Neurology, St. Joseph Hospital Berlin-Weißensee, Berlin, Germany.
Introduction: Parkinson's disease is a chronic neurodegenerative disease entity characterized by heterogeneity of symptoms and progression. Levodopa is an efficacious and well tolerated dopamine substituting drug for its therapy. Its O-methylation and generation of 3-O-methyldopa is enhanced by levodopa/dopa decarboxylase inhibitor formulations.
View Article and Find Full Text PDFJ Med Chem
October 2024
CIQUP-IMS/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto 4169-007, Portugal.
A new library of non-nitrocatechol compounds (HetCAMs) was developed and their efficacy was compared to tolcapone, a standard COMT inhibitor for PD. Compound emerged as the most potent inhibitor, showing selective inhibition of brain (IC = 24 nM) and liver (IC = 81 nM) MB-COMT over liver S-COMT (IC = 620 nM) isoforms. Although compound presented higher IC values than tolcapone, it was more selective for brain MB-COMT than liver S-COMT.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Department of Integrative Biotechnology, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983, Republic of Korea.
Comprehending early amyloidogenesis is essential for the development of effective therapeutic strategies. In tauopathies like Alzheimer's disease (AD), the abnormal accumulation of tau protein is initiated by pathological tau seeds. Mounting evidence implies that the microtubule binding domain, consisting of three to four repeats, plays a pivotal role in this process, yet the exact region driving the formation of pathogenic species needs to be further scrutinized.
View Article and Find Full Text PDFNeurol Ther
August 2024
Content and Communication, Branded Products, Orion Pharma, Orionintie 1, 02101, Espoo, Finland.
In the 1980s, Orion Pharma, then a mid-ranking Nordic area pharmaceutical company, established a drug development programme on the inhibition of catechol O-methyltransferase (COMT). This enzyme, which plays an important role in the inactivation of catecholamine neurotransmitters and drugs with a catechol structure, thus came under consideration as a target in the innovative translational and clinical programme we describe in this historical review. The starting point was the conjecture that a peripherally acting COMT inhibitor might improve entry of levodopa into the brain.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
May 2024
CIQUP-IMS - Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, R. Campo Alegre s/n, Porto 4169-007, Portugal.
Nitrocatechols are the standard pharmacophore to develop potent tight-binding inhibitors of catechol -methyltransferase (COMT), which can be used as coadjuvant drugs to manage Parkinson's disease. Tolcapone is the most potent drug of this class, but it has raised safety concerns due to its potential to induce liver damage. Tolcapone-induced hepatotoxicity has been attributed to the nitrocatechol moiety; however, other nitrocatechol-based COMT inhibitors, such as entacapone, are safe and do not damage the liver.
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