TY - JOUR. T1 - Contribution of catechol O-methyltransferase to the removal of accumulated interstitial catecholamines evoked by myocardial ischemia. AU - Kuroko, Yosuke. AU - Fujii, Takafumi. AU - Yamazaki, Toji. AU - Akiyama, Tsuyoshi. AU - Ishino, Kozo. AU - Sano, Shunji. AU - Mori, Hidezo. PY - 2005/11/11. Y1 - 2005/11/11. N2 - Catechol O-methyltransferase (COMT) plays an important role for clearance of high catecholamine levels. Although myocardial ischemia evokes similar excessive catecholamine accumulation, it is uncertain whether COMT activity is involved in the removal of accumulated catecholamines evoked by myocardial ischemia. We examined how COMT activity affects myocardial catecholamine levels during myocardial ischemia and reperfusion. We implanted a dialysis probe into the left ventricular myocardial free wall and measured dialysate catecholamines levels in anesthetized rabbits. Dialysate catecholamine levels served as an index of myocardial interstitial catecholamine levels. We ...
TY - JOUR. T1 - L-DOPA biotransformation. T2 - Correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients. AU - Dousa, M. K.. AU - Weinshilboum, Richard M. AU - Muenter, M. D.. AU - Offord, K. P.. AU - Decker, P. A.. AU - Tyce, G. M.. PY - 2003/8/1. Y1 - 2003/8/1. N2 - The objectives of this study were to determine (1) the effects of dose and drug absorption on pathways of biotransformation of L-DOPA in Parkinsonian patients treated with Sinemet, and (2) the extent to which genetically-determined variations in the activities of erythrocyte catechol O-methyltransferase and/or platelet phenol sulfotransferase might be reflected in individual differences in L-DOPA metabolism. In the 19 patients studied, there were negative correlations between dosage or absorption and extent of O-methylation and of sulfation of L-DOPA or its metabolites. Levels of activity for erythrocyte COMT were also reflected in individual ...
TY - JOUR. T1 - The catechol-O-methyltransferase polymorphism. T2 - Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. AU - Bilder, Robert M.. AU - Volavka, Jan. AU - Lachman, Herbert M.. AU - Grace, Anthony A.. PY - 2004/11/1. Y1 - 2004/11/1. N2 - Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val158Met polymorphism have been reported. We suggest that some of the complex effects of this polymorphism be understood from the perspective of the tonic-phasic dopamine (DA) hypothesis. We hypothesize that the COMT Met allele (associated with low enzyme activity) results in increased levels of tonic DA and reciprocal reductions in phasic DA in subcortical regions and increased D1 transmission cortically. This pattern of effects is hypothesized to yield increased stability but decreased flexibility of neural network activation states that underlie important aspects of working memory and executive functions; these effects may be beneficial or ...
TY - JOUR. T1 - A single-nucleotide polymorphism in the fetal catechol-o-methyltransferase gene is associated with spontaneous preterm birth in African Americans. AU - Thota, Chandrasekhar. AU - Menon, Ramkumar. AU - Wentz, Melissa J.. AU - Fortunato, Stephen J.. AU - Bartlett, Jackie. AU - Drobek, Cayce O.. AU - Nair, Sangeeta. AU - Al-Hendy, Ayman. PY - 2012/2. Y1 - 2012/2. N2 - Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than Caucasians (Cau). COMT converts 2- and 4-hydroxy (OH) estrogens to 2- and 4-methoxyestrogens, respectively, and can increase estrogenic milieu locally in tissues. To assess whether the increased incidence of preterm birth (PTB) among AA women is associated with single-nucleotide polymorphism (SNP) in the COMT gene, we examined variations in maternal and fetal COMT genes and their association with pregnancy outcomes (term vs preterm pregnancies) using 4 functional SNPs: rs4633, rs4680, rs4818, and rs6269 in both AA ...
BACKGROUND: Catechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val(158)Met polymorphism influences its activity, and multiple neural correlates of this genotype on dopaminergic phenotypes, especially working memory, have been reported. COMT activity can also be regulated pharmacologically by COMT inhibitors. The inverted-U relationship between cortical dopamine signaling and working memory predicts that the effects of COMT inhibition will differ according to COMT genotype. METHODS: Thirty-four COMT Met(158)Met (Met-COMT) and 33 COMT Val(158)Val (Val-COMT) men were given a single 200-mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a randomized, double-blind, between-subjects design. They completed the N-back task of working memory and a gambling task. RESULTS: In the placebo group, Met-COMT subjects outperformed Val-COMT subjects on the 2- back, and they were more risk averse. Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance
Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is one of several enzymes that degrade catecholamines (such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structure. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene. Two isoforms of COMT are produced: the soluble short form (S-COMT) and the membrane bound long form (MB-COMT). As the regulation of catecholamines is impaired in a number of medical conditions, several pharmaceutical drugs target COMT to alter its activity and therefore the availability of catecholamines. COMT was first discovered by the biochemist Julius Axelrod in 1957. Catechol-O-methyltransferase is involved in the inactivation of the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine). The enzyme introduces a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAM). Any compound having a catechol structure, like catecholestrogens and ...
The prefrontal cortex (PFC) dopamine system, which is critical for modulating PFC function, undergoes remodeling until at least young adulthood in primates. Catechol-o-methyltransferase (COMT) alters extracellular dopamine levels in PFC, and its gene contains a functional polymorphism (Val(158)Met) that has been associated with variation in PFC function. We examined COMT enzyme activity and protein immunoreactivity in the PFC during human postnatal development. Protein was extracted from PFC of normal individuals from 6 age groups: neonates (1-4 months), infants (5-11 months), teens (14-18 years), young adults (20-24 years), adults (31-43 years), and aged individuals (68-86 years; n = 5-8 per group). There was a significant 2-fold increase in COMT enzyme activity from neonate to adulthood, paralleled by increases in COMT protein immunoreactivity. Furthermore, COMT protein immunoreactivity was related to Val(158)Met genotype, as has been previously demonstrated. The significant increase in COMT activity
Catechol-O-methyltransferase (COMT Val158Met) has been implicated in both depression and cardiovascular disease. The purpose of this study was to assess if COMT Val158Met, which influences the COMT enzyme activity, has an effect on the risk of cardiovascular disease (CVD) in individuals with a history of depression and also to determine if the risk differs depending on gender. Data from a longitudinal cohort study of mental health among Swedish adults was used. Depression was assessed twice 3 years apart for each participant, in 1998-2001 and 2001-2003. Saliva DNA was contributed by 4349 (41.7%) of the participants and 3525 was successfully genotyped for COMT Val158Met. Participants were followed up until December 2014 from the National Patient register with regard to cardiovascular outcomes (hypertensive or ischemic heart disease, and stroke). Those with depression and the high COMT enzyme activity genotype (Val/Val) had almost a three-fold increased risk of later CVD (OR 3.6; 95% CI: 2.0-6.6) compared
The effect of catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain structure and function has been previously investigated separately and regionally; this prevents us from obtaining a full picture of the effect of this gene variant. Additionally, gender difference must not be overlooked because estrogen exerts an interfering effect on COMT activity. We examined 323 young healthy Chinese Han subjects and analyzed the gray matter volume (GMV) differences between Val/Val individuals and Met carriers in a voxel-wise manner throughout the whole brain. We were interested in genotype effects and genotype x gender interactions. We then extracted these brain regions with GMV differences as seeds to compute resting-state functional connectivity (rsFC) with the rest of the brain; we also tested the genotypic differences and gender interactions in the rsFCs. Val/Val individuals showed decreased GMV in the posterior cingulate cortex (PCC) compared with Met carriers; decreased GMV in the medial ...
... Catechol-O-methyltransferase Identifiers Symbol(s) COMT; External IDs OMIM: 116790 MGI: 88470 Homologene: 30982
We investigated whether the val(158)met functional polymorphism of catechol-o-methyltransferase influenced age-related changes in grey matter density and volume, both in healthy individuals (n=80, ages 18-79) and those with Parkinsons disease (n=50). Global grey matter volumes and voxelwise estimates of grey matter volume and density were determined from structural magnetic resonance images at 3T. Male and female ValVal homozygotes (low prefrontal cortical dopamine) had more grey matter in early adulthood, but this difference disappeared with increasing age. The insula and ventral prefrontal cortex had higher grey matter volume in younger, but not older, ValVal homozygotes. Conversely, the dominant premotor cortex revealed genotypic differences in grey matter density in later life. There were no global or local interactions between Parkinsons disease and COMT val(158)met genotype on morphometry. Since the val(158)met polymorphism is associated with differences in cortical dopamine metabolism, our data
Dose-response curves of increase in pupil size and decrease in intraocular pressure with topical epinephrine have been determined in the sympathetically denervated rabbit eye. Topical pretreatment with the catechol-O-methyl transferase inhibitor U-0521 potentiated the effects of epinephrine on both the pupil and pressure. These observations suggest a possible role for catechol-O-methyl transferase in the aqueous humor dynamics of the supersensitive eye. The possible use of the denervated rabbit eye as an experimental model for the glaucomatous eye in evaluating the ocular effects of adrenergic agents is discussed.. ...
Catechol-O-methyltransferase (COMT) modulates dopamine in the prefrontal cortex (PFC) and influences PFC dopamine-dependent cognitive task performance. A human COMT polymorphism (Val(158)Met) alters enzyme activity and is associated with both the activation and functional connectivity of the PFC during task performance, particularly working memory. Here, we used functional magnetic resonance imaging and a data-driven, independent components analysis (ICA) approach to compare resting state functional connectivity within the executive control network (ECN) between young, male COMT Val(158) (n=27) and Met(158) (n=28) homozygotes. COMT genotype effects on grey matter were assessed using voxel-based morphometry. COMT genotype significantly modulated functional connectivity within the ECN, which included the head of the caudate, and anterior cingulate and frontal cortical regions. Val(158) homozygotes showed greater functional connectivity between a cluster within the left ventrolateral PFC and the rest of
Catechol O-methyltransferase (COMT) is a ubiquitous bisubstrate magnesium-dependent enzyme found in plants, animals and microorganisms. COMT catalyses the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to one of the hydroxyl oxygen atoms (preferentially the 3-hydroxyl) in a catechol substrate. Physiological substrates of COMT are catecholamine neurotransmitters such as dopamine, noradrenaline, adrenaline and their metabolites. COMT also methylates catecholic steroids such as 2-hydroxyestradiol as well as a range of other catecholic compounds including neuroactive drugs such as L-dopa, α-methyldopa and isoproterenol. COMT inhibition is a means of treating Parkinsons disease, schizophrenia and depression. There are two isoforms of human COMT: soluble cytoplasmic COMT (S-COMT), which is mainly intracellular, and a membrane-bound form (MB-COMT), which has a single-span helix contained within a 50 amino acid extension at the N-terminus.. COMT is an enzyme that plays a major role in ...
Demethylzeylasteral is among the extracts of Hook F, which has important assignments in multiple biological procedures such as irritation inhibition, aswell as immunosuppression. thus inhibits its ubiquitin-dependent degradation. Jointly, demethylzeylasteral is normally a appealing anti-tumor substance in melanoma cells. Demethylzeylasteral can be a potential inhibitor of MCL1. Melanoma can be known as malignant melanoma from melanocytes.1 Surgical resection may be the main way for sufferers NSC 105823 struggling early-stage melanoma.1, 2 Unfortunately, melanoma lesions always stay undetectable,3 which leads to the hold off for melanoma therapy.4, 5 Moreover, melanoma may break out NSC 105823 in later levels,6 when melanoma cells disseminate to varied organs, such as for example human brain, lung or liver organ.2 Consequently, surgical procedure is much less favorable for sufferers. Chemotherapeutic therapy has an important function in cases like this. Theoretically, chemotherapeutic agents ...
Objective The principal goal of the study was to check the disease-modifying aftereffect of blocking a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 using a neutralizing monoclonal antibody (mAb) starting four weeks after destabilization from the medial meniscus (DMM) in the mouse. 4-16 after medical procedures slowed cartilage degeneration and osteophyte growth but did not impact subchondral bone sclerosis. Moreover, ADAMTS-5 blockade resulted in temporary reversal of mechanical allodynia, which correlated with decreased MCP-1 production by cultured DRG cells. Conclusions This study suggests restorative effectiveness of an ADAMTS-5 mAb in the DMM model, when therapy starts early in disease. mice demonstrate long-term safety from cartilage degeneration in experimental OA induced by destabilization of the medial meniscus (DMM) [6] and in antigen-induced arthritis (AIA) [7]. Mechanical allodynia, defined as pain in response to a normally innocuous stimulus, is definitely ...
OBJECTIVE: A valine/methionine polymorphism in the catechol O-methyltransferase (COMT) gene has been proposed to influence susceptibility to schizophrenia, as has a COMT haplotype in Ashkenazi Jewish and Irish subjects. The authors examined these hypotheses. METHOD: They reviewed data from more than 2,800 individuals, including almost 1,200 with schizophrenia, from case-control and family-based European association samples. RESULTS: The authors found no support for the hypothesis that a valine/methionine polymorphism in the COMT gene influences susceptibility to schizophrenia or the hypothesis that a COMT haplotype influences susceptibility to schizophrenia in Ashkenazi Jewish and Irish subjects. CONCLUSIONS: The data suggest that the valine allele of COMT does not increase susceptibility to schizophrenia in Europeans and that the Ashkenazi or Irish haplotype does not increase susceptibility. Ethnic variation in the linkage disequilibrium structure at COMT means that the haplotype data may not ...
Both childhood trauma and a functional COMT genetic polymorphism have been associated with PTSD and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n=38, Met carriers, n=35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD
In the previous post, we investigated the SLC6A4 gene, which is located on the 17th human chromosome, and has a possible (but, at the current time a statistically questionable) preference towards being expressed in ADHD males than in ADHD females.. The second gene on the list, the COMT gene, is also believed to have a male-favoring genetic effect with regards to ADHD individuals. The COMT gene is located on the 22nd human chromosome. "COMT" is actually an abbreviation for catechol methyltransferase, which is an important enzyme involved in a number of neurological functions which have numerous ADHD-like implications. This important enzyme is coded for by the COMT gene (many genes share a name with the proteins which they encode). Unlike the SLC6A4 gene, this COMT gene has more grounds for statistical significance, both in gender-dependent and overall studies of genes believed to be associated with ADHD.. We have discussed the COMT gene and its role in ADHD in previous posts. We have also ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
BACKGROUND: Neuregulin1 (NRG1)-ErbB signaling has been implicated in the pathogenesis of cancer and schizophrenia. We have previously reported that NRG1-stimulated migration of B lymphoblasts is PI3K-AKT1dependent and impaired in patients with schizophrenia and significantly linked to the catechol-o-methyltransferase (COMT) Val108/158Met functional polymorphism. METHODOLOGY/PRINCIPAL FINDINGS: We have now examined AKT1 activation in NRG1-stimulated B lymphoblasts and other cell models and explored a functional relationship between COMT and AKT1. NRG1-induced AKT1 phosphorylation was significantly diminished in Val carriers compared to Met carriers in both normal subjects and in patients. Further, there was a significant epistatic interaction between a putatively functional coding SNP in AKT1 (rs1130233) and COMT Val108/158Met genotype on AKT1 phosphorylation. NRG1 induced translocation of AKT1 to the plasma membrane also was impaired in Val carriers, while PIP(3) levels were not decreased. Interestingly
Catechol-O-methyltransferase (COMT) is involved in phase II (conjugative) metabolism of catecholamines and catechol drugs, such as dopamine, as well as the catechol-estrogens. COMT transfers a donor methyl-group from S-adenosylmethionine to acceptor hydroxy groups on catechol structures (aromatic ring structures with vicinal hydroxy-groups).(1) Bioactive catecholamine metabolites are metabolized by COMT in conjunction with monoamine oxidase (MAO):. -Norepinephrine is methylated by COMT forming normetanephrine.. -Epinephrine is methylated by COMT forming metanephrine.. -Dopamine is converted to homovanillic acid through the combined action of MAO and COMT.. Parkinsonism patients receiving levodopa (L-DOPA) therapy are frequently also prescribed a COMT inhibitor to minimize metabolism of L-DOPA by COMT, thereby prolonging L-DOPA action.. COMT is also involved in the inactivation of estrogens. Estradiol can be hydroxylated forming the catechol estrogens 2-hydroxyestradiol and 4-hydroxyestradiol.(2) ...
TY - JOUR. T1 - MB-COMT promoter DNA methylation is associated with working-memory processing in schizophrenia patients and healthy controls. AU - Walton, Esther. AU - Liu, Jingyu. AU - Hass, Johanna. AU - White, Tonya. AU - Scholz, Markus. AU - Roessner, Veit. AU - Gollub, Randy. AU - Calhoun, Vince D. AU - Ehrlich, Stefan. PY - 2014/8. Y1 - 2014/8. N2 - Many genetic studies report mixed results both for the associations between COMT polymorphisms and schizophrenia and for the effects of COMT variants on common intermediate phenotypes of the disorder. Reasons for this may include small genetic effect sizes and the modulation of environmental influences. To improve our understanding of the role of COMT in the disease etiology, we investigated the effect of DNA methylation in the MB-COMT promoter on neural activity in the dorsolateral prefrontal cortex during working memory processing as measured by fMRI - an intermediate phenotype for schizophrenia. Imaging and epigenetic data were measured in ...
Catechol-O-methyltransferase (COMT) catabolises the catecholamine neurotransmitters and influences cognitive function. COMT modulates dopamine levels in the prefrontal cortex and its action in this region is generally invoked to explain its effects on cognition. However, its role in other brain regions important for cognitive function remains largely unexplored. Here, we investigated COMTs impact on dopamine metabolism in the hippocampus and hippocampal-dependent behaviour. We examined the acute effects of a centrally-acting COMT inhibitor, tolcapone (30 mg/kg i.p.), on dopamine metabolism in the rat dorsal hippocampus, assessed both in tissue homogenates and extracellularly, using in vivo microdialysis. Additionally, we investigated the effect of tolcapone on delayed-rewarded alternation and spatial novelty preference, behavioural tasks which are dependent on the dorsal hippocampus. Tolcapone significantly modulated dopamine metabolism in the dorsal hippocampus, as indexed by the depletion of
Catechol-O-methyltransferase (COMT) plays an essential role in degradation of extracellular dopamine in prefrontal regions of the brain. Although a polymorphism in this gene, COMT Val(158)Met, affects human behavior in response to stress little is known about its effect on dopaminergic activity associated with the human stress response, which may be of interest for stress-related psychiatric disorders such as psychosis. We aimed to investigate the effect of variations in COMT genotype on in vivo measures of stress-induced prefrontal cortex (PFC) dopaminergic processing and subjective stress responses. A combined sample of healthy controls and healthy first-degree relatives of psychosis patients (n = 26) were subjected to an [(18)F]fallypride Positron Emission Tomography scan. Psychosocial stress during the scan was induced using the Montreal Imaging Stress Task and subjective stress was assessed every 12 minutes. Parametric t-maps, generated using the linear extension of the simplified reference ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
5 Dopamine Agonists Dopamine agonists directly stimulate the dopamine receptors, with bromocriptine (Parlodel®) and pergolide (Permax®) having been available in Canada for the treatment of PD for many years. More recently, two newer dopamine agonists - ropinirole (Requip®) and pramipexole (Mirapex®) - have become available. These differ from the older compounds in that they are not ergot derivatives, and are therefore devoid of ergot-related side effects such as retroperitoneal or pleural fibrosis. 3 Catechol-O-Methyl Transferase (COMT) Inhibitors Levodopa is metabolized peripherally not only by decarboxylase (as described above) but also by COMT. The latter is a ubiquitous enzyme, and is sufficiently active that when levodopa is administered with a peripheral decarboxylase inhibitor, only about 10% of a given dose will reach the brain intact [15]. Entacapone (Comtan®) inhibits the peripheral metabolism of levodopa by COMT, thereby increasing its availability to the brain, and increasing ...
Introduction: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. Methods: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2822 individuals. Results: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of ,= 1 fracture was 37.2% in COMTLL, 35.7% in COMTHL and 30.4% in COMTHH (p,0.05). Early fractures (,= 50 years of age) were less common in COMTHH than in the combined COMTLL+HL genotype, ...
Teva-Entacapone: Entacapone belongs to a group of medications called catechol-O-methyl transferase (COMT) inhibitors. It is used along with levodopa-carbidopa or levodopa-benserazide to treat Parkinsons disease.
Received within 4 weeks of Visit 1 or planning to take during participation in the clinical study: any doses of a controlled-release (CR) LD apart from a single daily bedtime dose or any doses of Rytary, additional CD (eg, Lodosyn) or benserazide (eg, Serazide), or catechol-O-methyl transferase inhibitors (entacapone or tolcapone) or medications containing these inhibitors (Stalevo). Received within 4 weeks of Visit 1 or planning to take during participation in the clinical study: nonselective monoamine oxidase (MAO) inhibitors, apomorphine, or dopaminergic blocking agents including antiemetics ...
1292] Mattay, V. S., Goldberg T. E., Fera F., Hariri A. R., Tessitore A., Egan M. F., et al. (2003). Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proceedings of the National Academy of Sciences of the United States of America. 100(10), 6186 - 6191. ...
Quercetin and fisetin, known as catechol-containing flavonoids, could positively affect the absorption of catechins due to their strong affinity for catechol-O-methyl transferase (COMT), which can methylate and cause the excretion of catechins. The current study examined the effect of quercetin and fisetin o
Using an isolated canine heart preparation, the myocardial norepinephrine pool was labeled by injecting tritiated norepinephrine into the blood perfusing the heart. The extraction of the norepinephrine during a single circulation through the coronary bed was shown to be large (74%). As the isotopic material, which was extracted, was released spontaneously from the norepinephrine pool 75% to 88% of it was metabolized before appearing in the coronary venous blood. The chief metabolite has been demonstrated to be normetanephrine which accounts for 39.0% to 61.7% of the spontaneously released norepinephrine. Because of this it is concluded that catechol-O-methyl transferase is the enzyme primarily responsible for the metabolic inactivation of norepinephrine in the canine heart. When release was increased by the injection of tyramine, more of the released norepinephrine appeared unmetabolized in coronary venous blood, suggesting that the enzymatic process by which norepinephrine is inactivated may be ...
Nedić, Gordana and Matea Nikolac, Matea and Borovečki, Fran and Hajnšek, Sanja and Muck-Šeler, Dorotea and Pivac, Nela (2010) Association study of a functional catechol-o-methyltransferase polymorphism and smoking in healthy Caucasian subjects. Neuroscience Letters, [Epub . ISSN 0304-3940 ...
The stress of foot shock in rats induces large decreases in the level of brain norepinephrine but does not greatly alter the concentration of serotonin or dopamine in brain. These decrements in norepinephrine are not limited to any region and occur uniformly throughout the brain. However, absolute levels of these amines are not a true indicator of their dynamic state. By various techniques it could be demonstrated that the stress of foot shock accelerates the metabolism of dopamine and serotonin to the same degree as norepinephrine; the only difference being that dopamine and serotonin are rapidly resynthesized, whereas norepinephrine in the brain cannot be regenerated at the same rate. Furthermore, the increased catabolism of brain norepinephrine with stress is blocked by monoamine oxidase inhibitors, whereas catechol-O-methyltransferase inhibitors do not impede accelerated degradation.. ...
Parkinsons disease is a progressive degenerative disorder of the central nervous system. The hallmark physical signs are tremor, rigidity and bradykinesia. Idiopathic Parkinsons disease is caused by the progressive loss of dopaminergic neurons in the substantia nigra and nigrostriatal pathway of the midbrain. Secondary parkinsonism may be caused by certain drugs (e.g., metoclopramide and haloperidol) or by cerebrovascular disease (e.g., multiple lacunar strokes). The disease can usually be diagnosed based on the history and physical findings. Dopamine replacement is still considered the most efficacious treatment for Parkinsons disease, but dopamine agonists, formerly prescribed only as adjunctive therapy, are emerging as useful initial therapy. Other pharmacologic treatments include drugs that inhibit dopamine-metabolizing enzymes (monoamine oxidase-B and catechol O-methyltransferase). Injections of botulinum toxin can be helpful in patients with associated dystonia or blepharospasm. Surgery may be
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Psychopharmacological modulation of the catecholaminergic system can enhance some aspects of cognitive function. For example, COMT inhibitors can slightly improve working memory/executive function. Similarly, modafinil, a catecholaminergic agonist that increases extracellular dopamine in the prefrontal cortex was also shown to improve delay-dependent working memory. Differences in the response between individuals might be related to a number of factors, including variations in the genes. The recent finding that a polymorphism in the catechol-o-methyl-transferase (COMT) gene, which produces a 4 fold change in enzyme activity, accounts for 4% of the variance in performance of working memory tasks in humans suggest that COMT genotype may predict response to COMT inhibitors or to other agonists that increase catecholaminergic function in the frontal cortex.. In the present investigation our goal is to examine, in normal controls and patients with schizophrenia, the effect of modafinil, a drug that ...
Objective: Little is known about genetic contributions to individual differences in cognitive plasticity. Given that the neurotransmitter dopamine is critical for cognition and associated with cognitive plasticity, we investigated the effects of 3 polymorphisms of dopamine-related genes (LMX1A, DRD2, COMT) on baseline performance and plasticity of working memory (WM), perceptual speed, and reasoning. Method: One hundred one younger and 103 older adults underwent approximately 100 days of cognitive training, and extensive testing before and after training. We analyzed the baseline and posttest data using latent change score models. Results: For working memory, carriers of the val allele of the COMT polymorphism had lower baseline performance and larger performance gains from training than carriers of the met allele. There was no significant effect of the other genes or on other cognitive domains. Conclusions: We relate this result to available evidence indicating that met carriers perform better ...
Children reporting psychotic experiences (PEs) are at increased risk of developing psychosis in adulthood. Cognitive deficits and anxiety disorders often precede psychotic disorders and are associated with higher risk of PEs. While the high activity alleles of variants within COMT have been associated with cognitive deficits, and the low activity alleles with higher risk of anxiety disorders, no associations of COMT with PEs have been found. One possible explanation is that the association between COMT and PEs is indirect, through cognitive function and anxiety disorders. We examined whether the association between PEs and COMT (four single nucleotide polymorphisms and three haplotypes) is indirect, through cognition or anxiety disorders. 6,784 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) were genotyped and completed neurocognitive assessments at ages 8 and 11, as well as semi-structured interviews for anxiety disorders and PEs at ages 10 and 12, respectively. ...
Dopamine metabolism in adults with 22q11 deletion syndrome, with and without schizophrenia--relationship with COMT Val¹⁰⁸/¹⁵⁸Met polymorphism, gender and symptomatology. - Erik Boot, Jan Booij, Nico Abeling, Julia Meijer, Fabiana da Silva Alves, Janneke Zinkstok, Frank Baas, Don Linszen, Thérèse van Amelsvoort
Wang, Y., Gau, Y,-T.A., Le, H.N.D., Bergles, D.E., Kang, J.U. (2017). Image analysis of dynamic brain activity based on gray distance compensation. Appl Sci, 7(8), 858.. Li, A., Liang, W., Guan, H., Gau, Y.-T.A., Bergles, D.E., and Li, X. (2017). Focus scanning with feedback-control for fiber-optic nonlinear endomicroscopy. Biomed Opt Express, 8(5), 2519-27.. Le, H.N.D., Gau, Y.-T.A., Rahmim, A., Wong, D.F., Kang, J.U., and Bergles, D.E. (2016). Through-skull vasculature assessment using fluorescence brain imaging on murine models at around 800 nm. Proc. SPIE 10051, Neural Imaging and Sensing, 10051-21.. Tsai, S.-J., Gau, Y.-T.A., Hong, C.-J., Liou, Y.-J., Yu, Y.W.-Y., Chen, T.-J., and Weissman, M.M. (2009). Sexually dimorphic effect of catechol-O-methyltransferase val158met polymorphism on clinical response to fluoxetine in major depressive patients. J. Affect. Disord. 113, 183-187.. Gau, Y.-T.A., Hong, C., and Tsai, S. (2008). Can antidepressants act as potential pro-neoplastic agents in ...
Section of Occupational and Environmental Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns ...
2008, Dilsat Ozkan Ariksoysal , Burcin Tezcanli , Buket Kosova,Mehmet Ozsoz ,Design of electrochemical biosensor systems for the detection of specific DNA sequences in PCR-amplified nucleic acids related to the catechol-O-methyltransferase val1 08/158Met polym val1 08/158Met polymorphism based on intrinsic guanine signal ,Anal.Chem. 80 , 3 : 588- ...
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The inhibition of soluble catechol-O-methyltransferase (S-COMT) in red blood cells (RBCs) by entacapone, and the pharmacokinetics of entacapone after singl
The present invention relates to 4-pyridinone compound as catechol -O- methyltransferase (COMT) inhibitors and are useful in the treatment or prevention of COMT enzyme is involved in neurological and psychiatric disorders and diseases. The present invention also relates to the use of these compounds comprises pharmaceutical compositions of these compounds and compositions in the prevention or disease involving COMT treatment.
1) It looks like the SNP in question does show some variation world wide. Europeans seem to have a higher frequency of the MET/MET genotype than Africans, while Asians tend to be lowest ...