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COMT INHIBITORS

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https://www.readbyqxmd.com/read/29107002/chronic-treatment-with-caffeine-and-its-withdrawal-modify-the-antidepressant-like-activity-of-selective-serotonin-reuptake-inhibitors-in-the-forced-swim-and-tail-suspension-tests-in-mice-effects-on-comt-slc6a15-and-adora1-gene-expression
#1
Aleksandra Szopa, Urszula Doboszewska, Mariola Herbet, Sylwia Wośko, Elżbieta Wyska, Katarzyna Świąder, Anna Serefko, Agnieszka Korga, Aleksandra Wlaź, Andrzej Wróbel, Marta Ostrowska, Joanna Terlecka, Adam Kanadys, Ewa Poleszak, Jarosław Dudka, Piotr Wlaź
Recent preclinical and clinical data suggest that low dose of caffeine enhances the effects of common antidepressants. Here we investigated the effects of chronic administration of caffeine (5mg/kg, twice daily for 14days) and its withdrawal on day 15th on the activity of per se ineffective doses of fluoxetine (5mg/kg) and escitalopram (2mg/kg) given on day 15th. We found decreased immobility time in the forced swim and tail suspension tests in mice in which caffeine was administered simultaneously with antidepressants on day 15th following a 14-day caffeine treatment and no alterations in the spontaneous locomotor activity...
December 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29074051/the-inhibitory-effects-of-%C3%AE-caryophyllene-%C3%AE-caryophyllene-oxide-and-%C3%AE-humulene-on-the-activities-of-the-main-drug-metabolizing-enzymes-in-rat-and-human-liver-in-vitro
#2
Linh Thuy Nguyen, Zuzana Myslivečková, Barbora Szotáková, Alena Špičáková, Kateřina Lněničková, Martin Ambrož, Vladimír Kubíček, Kristýna Krasulová, Pavel Anzenbacher, Lenka Skálová
Sesquiterpenes, the main components of plant essential oils, are often taken in the form of folk medicines and dietary supplements. Several sesquiterpenes possess interesting biological activities but they could interact with concurrently administered drugs via inhibition of drug-metabolizing enzymes. Therefore, the present study was designed to test the potential inhibitory effect of tree structurally relative sesquiterpenes β-caryophyllene (CAR), β-caryophyllene oxide (CAO) and α-humulene (HUM) on the activities of the main drug-metabolizing enzymes...
October 23, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29065678/bilateral-optic-neuropathy-related-to-severe-anemia-in-a-patient-with-alcoholic-cirrhosis-a-case-report-and-review-of-the-literature
#3
Lisa Humbertjean-Selton, Jérôme Selton, Nolwenn Riou-Comte, Jean-Christophe Lacour, Gioia Mione, Sébastien Richard
Anemia appears frequently in patients with alcoholic liver disease (ALD) but has never been linked to bilateral nonarteritic anterior ischemic optic neuropathy (NAION). A 65-year-old woman with a medical history of alcoholic cirrhosis was admitted for bilateral NAION. On admission, she was found to have a low arterial pressure and severe normocytic anemia (48 g/L). The anemia was related to chronic bleeding due to antral gastritis along with other factors associated with ALD. The applied treatment consisted of urgent transfusion followed by high doses of proton-pump inhibitors, iron and vitamin supplementation, and support in lifestyle measures...
October 25, 2017: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#4
REVIEW
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/29018243/6e11-a-highly-selective-inhibitor-of-receptor-interacting-protein-kinase-1-protects-cells-against-cold-hypoxia-reoxygenation-injury
#5
C Delehouzé, S Leverrier-Penna, F Le Cann, A Comte, M Jacquard-Fevai, O Delalande, N Desban, B Baratte, I Gallais, F Faurez, M C Bonnet, M Hauteville, P G Goekjian, R Thuillier, F Favreau, P Vandenabeele, T Hauet, M T Dimanche-Boitrel, S Bach
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28952032/neuroprotective-strategies-to-prevent-and-treat-parkinson-s-disease-based-on-its-pathophysiological-mechanism
#6
REVIEW
Yujeong Lee, Min-Sun Kim, Jaewon Lee
Parkinson's disease (PD) is the second most common progressive neurodegenerative disease after Alzheimer's disease. PD exhibits clinical symptoms that include tremors, rigidity, and bradykinesia. Many drugs are available to treat PD, such as, L-dopa, COMT inhibitor, MAO-B inhibitor, and dopamine agonists, but these drugs simply compensate for dopamine loss in PD, and therefore, cannot completely suppress its symptoms or progression. Although the causes of PD are not clearly understood, common pathophysiological pathways, such as, oxidative stress, mitochondrial dysfunction, and neuroinflammation are considered to be etiological factors, and thus, many treatments and interventions have been developed to target these pathophysiological factors...
September 26, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28916530/elucidation-of-the-impact-of-p-glycoprotein-and-breast-cancer-resistance-protein-on-the-brain-distribution-of-catechol-o-methyltransferase-inhibitors
#7
Joana Bicker, Ana Fortuna, Gilberto Alves, Patricio Soares-da-Silva, Amilcar Falcao
P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are clinically important efflux transporters that act cooperatively at the blood-brain barrier, limiting the entry of several drugs into the CNS and affecting their pharmacokinetics, therapeutic efficacy and safety. In the present study, the interactions of catechol-O-methyltransferase (COMT) inhibitors (BIA 9-1059, BIA 9-1079, entacapone, nebicapone, opicapone and tolcapone) with P-gp and BCRP were investigated in order to determine the contribution of these transporters in their access to the brain...
September 15, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28867940/genetics-of-generalized-anxiety-disorder-and-related-traits
#8
Michael G Gottschalk, Katharina Domschke
This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as pathological worry fear of uncertainty, and neuroticism. We inspect clinical genetic evidence for the familialityl heritability of GAD and cross-disorder phenotypes based on family and twin studies. Recent advances of linkage studies, genome-wide association studies, and candidate gene studies (eg, 5-HTT, 5-HT1A, MAOA, BDNF) are outlined. Functional and structural neuroimaging and neurophysiological readouts relating to peripheral stress markers and psychophysiology are further integrated, building a multilevel disease framework...
June 2017: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28844929/distribution-properties-and-inhibitor-sensitivity-of-zebrafish-catechol-o-methyl-transferases-comt
#9
Svetlana Semenova, Stanislav Rozov, Pertti Panula
Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is an enzyme with multiple functions in vertebrates. COMT methylates and thus inactivates catecholamine neurotransmitters and metabolizes xenobiotic catechols. Gene polymorphism rs4680 that influences the enzymatic activity of COMT affects cognition and behavior in humans. The zebrafish is widely used as an experimental animal in many areas of biomedical research, but most aspects of COMT function in this species have remained uncharacterized. We hypothesized that both comt genes play essential roles in zebrafish...
December 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28825621/inhibitory-effect-of-bovine-lactoferrin-on-catechol-o-methyltransferase
#10
Masayuki Ikeda, Hiroshi Iijima, Ichizo Shinoda, Hiroshi Iwamoto, Yasuhiro Takeda
Lactoferrin (LF) is a well-known multifunctional protein. In this study, we report the inhibitory potency of bovine LF (bLF) on catechol-O-methyltransferase (COMT), which catalyzes methylation of catechol substrates. We found that bLF binds to and inhibits COMT using its N-terminal region. An N-terminal peptide fragment obtained from bLF by trypsin digestion showed a higher inhibitory activity than intact bLF. A synthetic fragment of the bLF N-terminal residues 6-50, with two pairs of disulfide bonds, also showed higher inhibitory activity than intact bLF...
August 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28793366/cadmium-induced-melatonin-synthesis-in-rice-requires-light-hydrogen-peroxide-and-nitric-oxide-key-regulatory-roles-for-tryptophan-decarboxylase-and-caffeic-acid-o-methyltransferase
#11
Kyungjin Lee, Geun-Hee Choi, Kyoungwhan Back
In plants, melatonin production is induced by stimuli such as cold and drought, and cadmium (Cd) is the best elicitor of melatonin production in rice. However, the mechanism by which Cd induces melatonin synthesis in plants remains unknown. We challenged rice seedlings with Cd under different light conditions and found that continuous light produced the highest levels of melatonin, while continuous dark failed to induce melatonin production. Transcriptional and translational induction of tryptophan decarboxylase contributed to the light induction of melatonin during Cd treatment, whereas the protein level of light-induced caffeic acid O-methyltransferase (COMT) was decreased by Cd treatment...
August 9, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28768964/the-risk-factors-for-the-wearing-off-phenomenon-in-parkinson-s-disease-in-japan-a-cross-sectional-multicenter-study
#12
Shinji Ouma, Jiro Fukae, Shinsuke Fujioka, Shosaburo Yamamoto, Taku Hatano, Asako Yoritaka, Yasuyuki Okuma, Ken-Ichi Kashihara, Nobutaka Hattori, Yoshio Tsuboi
Objective Parkinson's disease (PD) is a common, progressive, neurodegenerative disorder. With progression of PD, the wearing-off phenomenon occurs more frequently as a motor complication, decreasing the patient's quality of life. The aim of this study was to investigate the risk factors for the wearing-off phenomenon in Japanese PD patients. Methods All of the study participants were clinically diagnosed as having PD. Each patient was assessed for the wearing-off phenomenon based on the findings of clinical assessments and interviews that were conducted during a single visit...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28746172/a-genetic-variant-in-the-catechol-o-methyl-transferase-comt-gene-is-related-to-age-dependent-differences-in-the-therapeutic-effect-of-calcium-channel-blockers
#13
Jiayue Xu, Adrian E Boström, Mohamed Saeed, Raghvendra K Dubey, Gérard Waeber, Peter Vollenweider, Pedro Marques-Vidal, Jessica Mwinyi, Helgi B Schiöth
Hypertension is the leading risk factor for cardiovascular disease and one of the major health concerns worldwide. Genetic factors impact both the risk for hypertension and the therapeutic effect of antihypertensive drugs. Sex- and age-specific variances in the prevalence of hypertension are partly induced by estrogen. We investigated 6 single nucleotide polymorphisms in genes encoding enzymes involved in estrogen metabolism in relation to sex- and age-specific differences in the systolic and diastolic blood pressure (SBP and DBP) outcome under the treatment of diuretics, calcium-channel blockers (CCBs), angiotensin-converting-enzyme inhibitors, and angiotensin-receptor blockers (ARBs)...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28734868/a-single-and-multiple-dose-study-to-investigate-the-pharmacokinetics-and-pharmacodynamics-of-opicapone-a-novel-comt-inhibitor-in-rat
#14
Daniela Gonçalves, Gilberto Alves, Ana Fortuna, Maria João Bonifácio, Patrício Soares-da-Silva, Amílcar Falcão
Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor that emerged to fulfil the need of a safer and more efficacious COMT inhibitor. The present study was carried out in order to assess and compare the pharmacokinetics and pharmacodynamics (COMT inhibition) of opicapone after single and multiple oral administrations (30 mg/kg) to Wistar rats. For this purpose, at predefined time points up to 72 h post-dosing, blood, liver and kidneys were collected and, then, the concentrations of opicapone and its active metabolite (BIA 9-1079) were determined in plasma and in liver and kidney tissues, as well as the erythrocyte, liver and kidney COMT activity...
July 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28715128/sibiriline-a-new-small-chemical-inhibitor-of-receptor-interacting-protein-kinase-1-prevents-immune-dependent-hepatitis
#15
Fabienne Le Cann, Claire Delehouzé, Sabrina Leverrier-Penna, Aveline Filliol, Arnaud Comte, Olivier Delalande, Nathalie Desban, Blandine Baratte, Isabelle Gallais, Claire Piquet-Pellorce, Florence Faurez, Marion Bonnet, Yvette Mettey, Peter Goekjian, Michel Samson, Peter Vandenabeele, Stéphane Bach, Marie-Thérèse Dimanche-Boitrel
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis...
September 2017: FEBS Journal
https://www.readbyqxmd.com/read/28611642/a-case-report-of-severe-delirium-after-amantadine-withdrawal
#16
Franz Marxreiter, Jürgen Winkler, Martin Uhl, Dominik Madžar
Amantadine is frequently used in addition to dopaminergic substances like dopamine agonists or L-Dopa in advanced Parkinson disease (PD). However, adverse effects like hallucinations limit its use. PD patients developing severe psychotic symptoms upon treatment with either dopaminergic substances and/or amantadine need to stop intake of any psychotropic substance. Here, we report the case of a 71-year-old PD patient without previously known cognitive impairment. He presented with drug-induced psychotic symptoms due to changes in his therapeutic regimen (increase in COMT inhibitors, newly introduced MAO B inhibitors)...
January 2017: Case Reports in Neurology
https://www.readbyqxmd.com/read/28580819/opicapone-for-the-management-of-end-of-dose-motor-fluctuations-in-patients-with-parkinson-s-disease-treated-with-l-dopa
#17
Andrew J Lees, Joaquim Ferreira, Olivier Rascol, Heinz Reichmann, Fabrizio Stocchi, Eduardo Tolosa, Werner Poewe
Opicapone is a third generation, highly potent and effective catechol O‑methyltransferase (COMT) inhibitor that optimizes the pharmacokinetics and bioavailability of L-DOPA therapy. Areas covered: In this review, the authors describe the preclinical and clinical development of opicapone. In PD patients with motor fluctuations, once daily opicapone administration was well-tolerated and consistently reduced OFF-time and increased ON-time without increasing the frequency of troublesome dyskinesia, and these benefits were maintained over at least a year of continued open-label therapy...
July 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28494719/levodopa-in-parkinson-s-disease-current-status-and-future-developments
#18
N Tambasco, M Romoli, P Calabresi
Ever since the pioneering reports in the 60s, L-3,4-Dioxyphenylalanine (levodopa) has represented the gold standard for the treatment of Parkinson's Disease (PD). However, long-term levodopa (LD) treatment is frequently associated with fluctuations in motor response, often challenging to resolve, with serious impact on patients quality of life. The pharmacokinetic and pharmacodynamics properties of LD are pivotal to such motor fluctuations: discontinuous drug delivery, short half-life, poor bioavailability, and narrow therapeutic window are all crucial for such fluctuations...
May 10, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28461606/catechol-o-methyltransferase-deficiency-leads-to-hypersensitivity-of-the-pressor-response-against-angiotensin-ii
#19
COMPARATIVE STUDY
Norikazu Ueki, Keizo Kanasaki, Megumi Kanasaki, Satoru Takeda, Daisuke Koya
Catechol-O-methyltransferase (COMT) metabolizes 2-hydroxyestradiol into 2-methoxyestradiol (2-ME); COMT deficiency has shown to be associated with hypertension in men and preeclampsia, the disease associated with hypersensitivity of pressor response against angiotensin II (Ang II). Here, we found that COMT deficiency could explain the hypersensitivity of pressor response against Ang II in mice because of the lack of 2-ME-dependent suppression of angiotensin II receptor type 1 (AT1R). Male C57BL/6 mice were subjected to COMT inhibitor (COMTi: 25 mg/kg per day) or oil (control) for 4 weeks, with or without low-dose Ang II infusion (ANGII: 70 ng/kg per minute) for the last 3 weeks...
June 2017: Hypertension
https://www.readbyqxmd.com/read/28429453/tolcapone-induces-oxidative-stress-leading-to-apoptosis-and-inhibition-of-tumor-growth-in-neuroblastoma
#20
Tyler Maser, Maria Rich, David Hayes, Ping Zhao, Abhinav B Nagulapally, Jeffrey Bond, Giselle Saulnier Sholler
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Tolcapone, a drug commonly used in the treatment of Parkinson's disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. In this study, we demonstrate that Tolcapone kills neuroblastoma (NB) cells in preclinical models by inhibition of COMT. Treating four established NB cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with IncuCyte imaging and Western blotting indicating that cell death was due to caspase-3-mediated apoptosis...
June 2017: Cancer Medicine
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