Analytical methodologies for sensing catechol-O-methyltransferase activity and their applications / 药物分析学报

Mammalian catechol-O-methyltransferases(COMT)are an important class of conjugative enzymes,which play a key role in the metabolism and inactivation of catechol neurotransmitters,catechol es-trogens and a wide range of endobiotics and xenobiotics that bear the catechol group.Currently,COMT inhibitors are used in combination with levodopa for the treatment of Parkinson's disease in clinical practice.The crucial role of COMT in human health has raised great interest in the development of more practical assays for highly selective and sensitive detection of COMT activity in real samples,as well as for rapid screening and characterization of COMT inhibitors as drug candidates.This review summarizes recent advances in analytical methodologies for sensing COMT activity and their applications.Several lists of biochemical assays for measuring COMT activity,including the probe substrates,along with their analytical conditions and kinetic parameters,are presented.Finally,the challenges and future perspec-tives in the field,such as visualization of COMT activity in vivo and in situ,are highlighted.Collectively,this review article overviews the practical assays for measuring COMT activities in complex biological samples,which will strongly facilitate the investigations on the relevance of COMT to human diseases and promote the discovery of COMT inhibitors via high-throughput screening.

Is There the Preventive Effect of COMT-inhibitor on Parkinson's Disease Associated with Dementia?

BACKGROUND: Elevated homocysteine (hcy) levels are associated with dementia, which is a frequent non-motor symptom of Parkinson's disease (PD). High levels of hcy in PD patients treated with levodopa are thought to result from increased synthesis during the metabolism of levodopa by COMT, and that use of a COMT-inhibitor may reduce hcy levels. In this study, we sought to clarify the effects of COMT-inhibitors on dementia in PD patients. METHODS: Thirty-eight PD patients without dementia (PDwoD), 35 PD patients with dementia (PDD), and 48 controls were enrolled in this study. All subjects underwent neuropsychological testing and a neurological examination. The hcy levels were measured in all subjects, and the relationship between hcy levels and dementia was evaluated in two PD groups (those that underwent treatment with levodopa-alone versus treatment with levodopa plus a COMT-inhibitor). RESULTS: Patients in the PDD group showed higher hcy levels than patients in the PDwoD group, though there was no significant difference in the hcy level between PDwoD patients and healthy controls. Regarding the effects of a COMT-inhibitor, there was no correlation between hcy levels in the 2 PD subgroups, indicating that there were no significant effects of the COMT-inhibitor on PDD. In addition, the odds ratio for PDD with the use of a COMT-inhibitor was 0.864 (95% CI=0.342-2.180). CONCLUSIONS: These results are in agreement with previous studies in that levodopa treatment in PD patients leads to elevated hcy concentrations. COMT-inhibitors, on the other hand, had no preventive effect on cognitive impairment in PD patients.