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COMT Inhibitors (comt + inhibitor)
Selected AbstractsSimultaneous analysis of catechol- O -methyl transferase activity, S -adenosylhomocysteine and adenosineBIOMEDICAL CHROMATOGRAPHY, Issue 3 2010Ilkka Reenilä Abstract Novel HPLC method utilizing UV-detection was developed to analyse catechol- O -methyltransferase (COMT) products, vanillic acid and isovanillic acid, S -adenosylhomocysteine (SAH) and adenosine formed from dihydroxybenzoic acid and S -adenosyl-L-methionine (SAM) by incubation of the rat tissues. Entacapone, a COMT inhibitor, prevented the formation of SAH only partially in the striatal homogenate whereas in the kidney homogenate the increase of SAH was prevented by entacapone. In conclusion, this method was reliable, rapid and simple. COMT seemed to be partially responsible on the SAM utilizing methylations in the striatal homogenates while in the high COMT activity tissue, COMT was the main SAH producing methyltransferase. Copyright © 2009 John Wiley & Sons, Ltd. [source] Tissue histopathology, clinical chemistry and behaviour of adult comt -gene-disrupted miceJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2003Kristiina Haasio Abstract Catechol- O -methyltransferase (COMT) enzyme is a widely distributed enzyme that catalyses O -methylation of catecholamines and other compounds having a catechol structure. Because there has been some concern about the consequences of a low COMT activity in the development of oestrogen-dependent cancers and because one of the COMT inhibitors, tolcapone, has caused serious liver injuries in Parkinsonian patients, the histopathology and clinical chemistry of Comt -gene-disrupted mice were studied at the age of 12 months. Owing to the high COMT activities in liver and kidney and the role of COMT in the metabolism of catechol oestrogens, special emphasis was given to the histology of the liver, kidney and oestrogen-dependent organs such as mammary glands and uterus. The mice of both heterozygous and homozygous genotypes appear to be physically healthy and fertile. Diurnal motility rhythm and behaviour in measuring anxiety and depression were equal in all genotypes. At the age of 12 months, the body weight of homozygous mice was 7,9% lower than that of the other groups. This was re,ected in histology as a diminished incidence of vacuolation of liver cells (fatty change). Macroscopic pathology and histopathology revealed no abnormal ,ndings in any COMT genotype. The values of some clinical chemistry parameters, such as alkaline phosphatase, alanine aminotransferase, urea, glucose, calcium and proteins, were at a higher level in homozygous animals compared with the wild-type mice. However, all the values remained within the normal physiological range, and the differences in enzyme levels between genotypes were not re,ected as histopathological ,ndings in the relevant organs. No changes in haematological parameters or plasma catecholamine concentrations were noted but plasma 3,4-dihydroxyphenylethylene glycol levels were high in COMT null mice. The results suggest that the full or 50% lack of Comt gene as such is not associated with any toxic consequences. Copyright © 2003 John Wiley & Sons, Ltd. [source] A 3-D QSAR Study of Catechol- O -Methyltransferase Inhibitors Using CoMFA and CoMSIAMOLECULAR INFORMATICS, Issue 10 2008Chunzhi Ai Abstract Inhibitors of Catechol- O -Methyltransferase (COMT) play an important role in the treatment of Parkinson's Disease (PD). A new Three-Dimensional Quantitative Structure,Activity Relationship (3-D QSAR) analysis was performed on 36 previously reported COMT inhibitors employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methodologies to correlate the molecular fields and percent inhibition values and three predictive models were derived. The CoMFA and CoMSIA models with steric and electrostatic field yielded cross-validated rs of 0.585 and 0.528, respectively whereas the conventional rs were 0.979 and 0.891, respectively. The CoMSIA model with hydrophobic field exhibited a r of 0.544 and a r of 0.930. The individual inspection of 3-D contours generated from these models helps in understanding the possible region for structural modification of molecules to improve the inhibitory bioactivity. These 3-D QSAR models are also useful for designing and predicting novel COMT inhibitors. [source] A rapid assay method for catechol- O -methyltransferase activity by flow injection analysisBIOMEDICAL CHROMATOGRAPHY, Issue 4 2002Nozomi Aoyama A rapid assay employing flow injection analysis (FIA) to determine the activity of purified catechol- O -methyltransferase (COMT) from porcine liver is described. The method was based on the determination of normetanephrine, the 3- O -methyl metabolite of the substrate norepinephrine. Excess norepinephrine was removed from the incubation mixture by alumina extraction twice to allow normetanephrine to be subjected to flow injection analysis, coulometrical oxidation, fluorogenic reaction with ethylenediamine and fluorescence detection. Km and Vmax values for COMT obtained with the system were 503,µM and 4.51 nmol/min/mg protein, respectively. The method is suitable for screening of COMT inhibitors or activators, as a large number of samples, up to 200, can be processed in one working day. Copyright © 2002 John Wiley & Sons, Ltd. [source] | ||||||||||