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Dextromethorphan

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https://www.readbyqxmd.com/read/28449367/metoprolol-pridopidine-drug-drug-interaction-and-food-effect-assessments-of-pridopidine-a-new-drug-for-treatment-of-huntington-disease
#1
Laura Rabinovich-Guilatt, Lilach Steiner, Hussein Hallak, Gina Pastino, Pierandrea Muglia, Ofer Spiegelstein
AIM: Pridopidine is an oral drug in clinical development for treatment of patients with Huntington disease. This study examined the interactions of pridopidine with in vitro cytochrome P450 activity and characterized the effects of pridopidine on CYP2D6 activity in healthy volunteers using metoprolol as a probe substrate. The effect of food on pridopidine exposure was assessed. METHODS: The ability of pridopidine to inhibit and/or induce in vitro activity of drug metabolising enzymes was examined in human liver microsomes and fresh hepatocytes...
April 27, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28448746/pharmaceutical-chemicals-steroids-and-xenoestrogens-in-water-sediments-and-fish-from-the-tidal-freshwater-potomac-river-virginia-usa
#2
Golala Arya, Sara Tadayon, James Sadighian, Jennifer Jones, Kim de Mutsert, Thomas B Huff, Gregory D Foster
Selected pharmaceutical chemicals, steroids and xenoestrogens (PCSXs) consisting of 29 endocrine modulators, therapeutic drugs, pesticides, detergents, plastics, and active ingredients in household products were measured in water, riverbed sediments and fish collected in a tributary embayment of the Potomac River (Hunting Creek, Alexandria, VA, USA) in the vicinity of wastewater discharge. A total of 17 PCSXs were found in the Hunting Creek samples, with steroid hormones (e.g., progesterone and 17α-ethinylestradiol), triclosan, dextromethorphan and bisphenol A being the most prominent micropollutants detected...
April 27, 2017: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/28413907/interaction-of-dextromethorphan-hydrobromide-with-dna-multispectral-voltammetric-and-molecular-docking-technology
#3
Shuyun Bi, Huifeng Zhou, Jun Wu, Yu Wang
No abstract text is available yet for this article.
April 16, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28396528/human-enterocytes-as-an-in-vitro-model-for-the-evaluation-of-intestinal-drug-metabolism-characterization-of-drug-metabolizing-enzyme-activities-of-cryopreserved-human-enterocytes-from-twenty-four-donors
#4
Ming-Chih David Ho, Nick Ring, Kirsten Amaral, Utkarsh Doshi, Albert Li
We report here successful isolation and cryopreservation of enterocytes from human small intestine. The enterocytes were isolated by enzyme digestion of the intestinal lumen followed by partial purification via differential centrifugation. The enterocytes were cryopreserved directly after isolation without culturing to maximize retention of in vivo drug metabolizing enzyme activities. Post-thaw viability of the cryopreserved enterocytes was consistently over 80% based on trypan blue exclusion. Cryopreserved enterocytes pooled from 8 donors (4 male and 4 female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), CYP2C9 (diclofenac 4-hydroxylation), CYP2C19 (s-mephenytoin 4-hydroxylation), CYP2D6 (dextromethorphan hydroxylation), CYP2E1 (chlorzoxazone 6-hydroxylation), CYP3A4 (midazolam 1'-hydroxylation and testosterone 6β-hydroxylation), CYP2J2 (astemizole O-demethylation), UDP-glucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7-hydroxycoumarin sulfation), and carboxylesterase 2 (CES2; irinotecan hydrolysis) activities...
April 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28377827/anti-yo-mediated-paraneoplastic-cerebellar-degeneration-associated-with-pseudobulbar-affect-in-a-patient-with-breast-cancer
#5
Allison N Martin, Patrick M Dillon, David E Jones, David R Brenin, David A Lapides
Paraneoplastic cerebellar degeneration (PCD) is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA). Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28376072/dextromethorphan-and-methylxanthines-might-be-useful-in-the-treatment-of-methotrexate-induced-neurotoxicity
#6
Francisco José Fernández-Fernández, Eugenia Ameneiros-Lago, Cristina Lijó-Carballeda, Pascual Sesma
No abstract text is available yet for this article.
April 4, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28370447/trial-of-dextromethorphan-quinidine-to-treat-levodopa-induced-dyskinesia-in-parkinson-s-disease
#7
Susan H Fox, Leonard Verhagen Metman, John G Nutt, Matthew Brodsky, Stewart A Factor, Anthony E Lang, Laura E Pope, Nadine Knowles, João Siffert
BACKGROUND: Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia. METHODS: PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout...
March 30, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28302194/-clinical-and-molecular-genetic-study-of-nonketotic-hyperglycinemia-in-a-chinese-family
#8
Zhi-Jie Gao, Qian Jiang, Qian Chen, Ke-Ming Xu
Nonketotic hyperglycinemia (NKH) is a rare, inborn error of metabolism. In this case report, a Chinese male infant was diagnosed with NKH caused by GLDC gene mutation. The clinical characteristics and genetic diagnosis were reported. The infant presented with an onset of early metabolic encephalopathy and Ohtahara syndrome. Both blood and urinary levels of metabolites were in the normal range. Brain MRI images indicated a poor development of corpus callosum, and a burst suppression pattern was found in the EEG...
March 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28300462/an-update-on-the-advancements-in-the-treatment-of-agitation-in-alzheimer-s-disease
#9
REVIEW
Anton P Porsteinsson, Inga M Antonsdottir
Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks safe and effective long term interventions. Nonpharmacological interventions are suggested as first-line treatment, but aren't effective for every patient, resulting in pharmacological interventions for some patients, consisting of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine, and antidepressants; where efficacy doesn't necessarily outweigh associated risks...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28290770/in-vivo-characterization-of-cyp2d6-12-29-and-84-using-dextromethorphan-as-a-probe-drug-a-case-report
#10
Andrea Gaedigk, Greyson P Twist, Emily G Farrow, Jennifer A Lowry, Sarah E Soden, Neil A Miller
CYP2D6*84 was first described in a Black South African subject, however, its function remains unknown. Astrolabe, a probabilistic scoring tool developed in our laboratory to call genotypes from whole genome sequence, identified CYP2D6*84 in a trio. The father presented with intermediate metabolism when challenged with the CYP2D6 probe drug dextromethorphan (DM/dextrorphan [DX] = 0.0839). Since his second allele, CYP2D6*12, is nonfunctional, the observed activity is derived by CYP2D6*84. This finding suggests that the allele's hallmark P267H causes decreased activity toward DM and that this allele should receive a value of 0...
March 14, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28288109/in-silico-design-of-novel-probes-for-the-atypical-opioid-receptor-mrgprx2
#11
Katherine Lansu, Joel Karpiak, Jing Liu, Xi-Ping Huang, John D McCorvy, Wesley K Kroeze, Tao Che, Hiroshi Nagase, Frank I Carroll, Jian Jin, Brian K Shoichet, Bryan L Roth
The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small-molecule MRGPRX2 agonists, selective nanomolar-potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found that many opioid compounds activated MRGPRX2, including (-)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan, and the prodynorphin-derived peptides dynorphin A, dynorphin B, and α- and β-neoendorphin...
May 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28271978/lessons-from-cuba-for-global-precision-medicine-cyp2d6-genotype-is-not-a-robust-predictor-of-cyp2d6-ultrarapid-metabolism
#12
Pedro Dorado, Idilio González, María Eugenia G Naranjo, Fernando de Andrés, Eva María Peñas-Lledó, Luis Ramón Calzadilla, Adrián LLerena
A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic and practical reasons. Moreover, an additional barrier for clinical implementation of precision medicine is the lack of correlation between genotype and phenotype, considering that most of the current methods include only genotyping...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28254952/effects-of-microrna-34a-on-the-pharmacokinetics-of-cytochrome-p450-probe-drugs-in-mice
#13
Joseph L Jilek, Ye Tian, Ai-Ming Yu
MicroRNAs (miRNAs or miRs), including miR-34a, have been shown to regulate nuclear receptor, drug-metabolizing enzyme, and transporter gene expression in various cell model systems. However, to what degree miRNAs affect pharmacokinetics (PK) at the systemic level remains unknown. In addition, miR-34a replacement therapy represents a new cancer treatment strategy, although it is unknown whether miR-34a therapeutic agents could elicit any drug-drug interactions. To address this question, we refined a practical single-mouse PK approach and investigated the effects of a bioengineered miR-34a agent on the PK of several cytochrome P450 probe drugs (midazolam, dextromethorphan, phenacetin, diclofenac, and chlorzoxazone) administered as a cocktail...
May 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28254772/central-inhibition-of-initiation-of-swallowing-by-systemic-administration-of-diazepam-and-baclofen-in-anaesthetized-rats
#14
Takanori Tsujimura, Shogo Sakai, Taku Suzuki, Izumi Ujihara, Kojun Tsuji, Jin Magara, Brendan J Canning, Makoto Inoue
Dysphagia is caused not only by neurological and/or structural damage but also by medication. We hypothesized memantine, dextromethorphan, diazepam and baclofen, all commonly used drugs with central sites of action, may regulate swallowing function. Swallows were evoked by upper airway (UA)/pharyngeal distension, punctate mechanical stimulation using a von Frey filament, capsaicin or distilled water (DW) applied topically to the vocal folds, and electrical stimulation of a superior laryngeal nerve (SLN) in anesthetized rats and were documented by recording electromyographic activation of the suprahyoid and thyrohyoid muscles and by visualizing laryngeal elevation...
March 2, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28211700/from-genotype-to-phenotype-cytochrome-p450-2d6-mediated-drug-clearance-in-humans
#15
Jie Gao, Xin Tian, Jun Zhou, Ming-Zhu Cui, Hai-Feng Zhang, Na Gao, Qiang Wen, Hai-Ling Qiao
How genotypic variation results in phenotypic differences is still a challenge for biology. In the field of drug metabolism, the means by which specific cytochrome P4502D6 (CYP2D6) genotypes yield different phenotypes at various levels (molecular, cellular, and organismal) is an important question, as differences in CYP2D6 activity can contribute to adverse drug reactions. Herein, the genotype of CYP2D6 was determined along with the absolute content of CYP2D6 and microsomal protein per gram of liver in human liver microsomes, the molecular, cellular (microsomal, tissue, organ), and organismal phenotype of CYP2D6 determined; the effect of genotype on each phenotype of CYP2D6-mediated dextromethorphan clearance (CL) was delineated, and the overall genotype-phenotype relationship for CYP2D6 was charted...
February 24, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28194724/ketamine-and-beyond-investigations-into-the-potential-of-glutamatergic-agents-to-treat-depression
#16
REVIEW
Marc S Lener, Bashkim Kadriu, Carlos A Zarate
Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder and bipolar depression. In clinical studies of individuals with major depressive disorder and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants...
March 2017: Drugs
https://www.readbyqxmd.com/read/28155129/drug-interaction-potential-of-osilodrostat-lci699-based-on-its-effect-on-the-pharmacokinetics-of-probe-drugs-of-cytochrome-p450-enzymes-in-healthy-adults
#17
Sara Armani, Lillian Ting, Nicholas Sauter, Christelle Darstein, Anadya Prakash Tripathi, Lai Wang, Bing Zhu, Helen Gu, Dung Yu Chun, Heidi J Einolf, Swarupa Kulkarni
BACKGROUND AND OBJECTIVES: Osilodrostat (LCI699) is an adrenal steroidogenesis inhibitor currently in late-phase clinical development as a potential treatment for Cushing's disease. This study evaluated the inhibitory effect of osilodrostat on the pharmacokinetics of probe substrates of the cytochrome P450 (CYP) enzymes CYP1A2, CYP2C19, CYP2D6, and CYP3A4. METHODS: Healthy adult volunteers received single-dose cocktail probe substrates [caffeine (100 mg), omeprazole (20 mg), dextromethorphan (30 mg), and midazolam (2 mg)] followed by a 6-day washout...
February 2, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28153746/dextromethorphan-upregulates-osteoblast-and-osteoclast-activity-but-does-not-attenuate-ovariectomy-induced-osteoporosis
#18
Jia-Lin Wu, Wei-Yuan Tsai, Jian-Horng Chen, Chih-Shung Wong
AIMS: Study on the in vivo regulatory role of glutamate in osteoblast (OB) and osteoclast (OC) differentiation is less advanced. The present study investigated the effect of dextromethorphan (DXM), an N-methyl-d-aspartate receptors (NMDARs) antagonist, on osteoporosis development. MAIN METHODS: In order to examine the role of glutamate in bone metabolism, ovariectomized (Ovx) female Wistar rats were injected three times per week for 8weeks with either saline, or 15μg/kg of β-estrodiol, or DXM (40mg/kg) intraperitoneally...
March 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28097507/in-vitro-phase-i-and-phase-ii-drug-metabolism-in-the-liver-of-juvenile-and-adult-g%C3%A3-ttingen-minipigs
#19
Els Van Peer, Frank Jacobs, Jan Snoeys, Jos Van Houdt, Ils Pijpers, Christophe Casteleyn, Chris Van Ginneken, Steven Van Cruchten
PURPOSE: In view of pediatric drug development, juvenile animal studies are gaining importance. However, data on drug metabolizing capacities of juvenile animals are scarce, especially in non-rodent species. Therefore, we aimed to characterize the in vitro biotransformation of four human CYP450 substrates and one UGT substrate in the livers of developing Göttingen minipigs. METHODS: Liver microsomes from late fetal, Day 1, Day 3, Day 7, Day 28, and adult male and female Göttingen minipigs were incubated with a cocktail of CYP450 substrates, including phenacetin, tolbutamide, dextromethorphan, and midazolam...
January 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28094924/reversible-and-selective-encapsulation-of-dextromethorphan-and-%C3%AE-estradiol-using-an-asymmetric-molecular-capsule-assembled-via-the-weak-link-approach
#20
Jose Mendez-Arroyo, Andrea I d'Aquino, Alyssa B Chinen, Yashin D Manraj, Chad A Mirkin
An allosterically regulated, asymmetric receptor featuring a binding cavity large enough to accommodate three-dimensional pharmaceutical guest molecules as opposed to planar, rigid aromatics, was synthesized via the Weak-Link Approach. This architecture is capable of switching between an expanded, flexible "open" configuration and a collapsed, rigid "closed" one. The structure of the molecular receptor can be completely modulated in situ through the use of simple ionic effectors, which reversibly control the coordination state of the Pt(II) metal hinges to open and close the molecular receptor...
February 1, 2017: Journal of the American Chemical Society
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