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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
#1
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
#2
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...
January 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28094079/a-stroke-mimic-methotrexate-induced-neurotoxicity-in-the-emergency-department
#3
Patrick Rogers, Wilbur J Pan, Richard A Drachtman, Christopher Haines
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia. The treatment of ALL involves multimodality therapy, and methotrexate (MTX) remains a mainstay of treatment. A complication of MTX therapy includes acute, subacute, and chronic neurotoxocity. Signs and symptoms may range from headaches, dizziness, and mood disorders to seizures and stroke-like symptoms. CASE REPORT: An 18-year-old woman with a history of ALL presented to the emergency department with acute onset of right-sided facial paralysis, right upper extremity flaccid paralysis, and right lower extremity weakness after receiving MTX therapy 3 days earlier...
January 13, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28070747/enhanced-bulbar-function-in-amyotrophic-lateral-sclerosis-the-nuedexta-treatment-trial
#4
Richard Smith, Erik Pioro, Kathleen Myers, Michael Sirdofsky, Kimberly Goslin, Gregg Meekins, Hong Yu, James Wymer, Merit Cudkowicz, Eric A Macklin, David Schoenfeld, Gary Pattee
The goal of this randomized, blinded, crossover clinical trial was to determine whether Nuedexta (dextromethorphan and quinidine) enhanced speech, swallowing, and salivation in patients with ALS. Sixty patients with amyotrophic lateral sclerosis (ALS) received either Nuedexta or placebo for 28 to 30 days, followed by a 10 to 15-day washout period. Subsequently, patients were switched to the opposite treatment arm for the remaining days of the trial. The primary endpoint was a reduction in the self-report Center for Neurologic Study Bulbar Function Scale (CNS-BFS) score...
January 9, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28057170/can-the-ceiba-cocktail-designed-for-human-cytochrome-p450-enzymes-be-used-in-the-rat-for-drug-interaction-studies
#5
Paulo Magalhães, Fernando De Andrés, Amílcar Falcão, Adrián LLerena, Gilberto Alves
Purpose - The CEIBA cocktail consisting of caffeine (CAF), omeprazole (OZ), dextromethorphan (DM) and losartan (LOS) was previously proposed for the clinical phenotyping of five major human cytochrome P450 (CYP) isoenzymes. This work aimed to assess the usefulness of CEIBA cocktail to study non-clinical drug interactions in the rat. Methods - Wistar rats were divided into five groups to receive a single-oral dose of each probe drug (CAF, OZ, LOS, DM), individually or in combination as a cocktail. Plasma concentrations of the probe drugs and their metabolites [paraxanthine (1,7-X), 5-hydroxyomeprazole (5-OZ), losartan carboxylic acid (E-3174), dextrorphan (DX) and 3-methoxymorphinan (3-MM)] were determined by LC-MS/MS, and the corresponding pharmacokinetic parameters were estimated by non-compartmental analysis...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28010169/consequences-of-daily-corticosteroid-dosing-with-or-without-pre-treatment-with-quinidine-on-the-in-vivo-cytochrome-p450-2d-cyp2d-enzyme-in-rats-effect-on-o-demethylation-activity-of-dextromethorphan-and-expression-levels-of-cyp2d1-mrna
#6
Poonam Giri, Prashant Delvadia, Laxmikant Gupta, Nirmal Patel, Priyal Trivedi, Krishna Lad, Hiren M Patel, Nuggehally R Srinivas
1. Present investigation was carried out in rats to study influence of corticosteroids after repeated dosing with/without pre-treatment with CYP2D inhibitor quinidine on the CYP2D1 mRNA levels and CYP2D enzyme activity using dextromethorphan as probe substrate. 2. CYP2D1 mRNA was measured in liver homogenate using quantitative real-time polymerase chain reaction [qRT-PCR] and enzymatic reaction was studied ex vivo in liver S-9 fractions of rats treated with oral 10 mg/kg dexamethasone or prednisolone for five days or pre-treated with quinidine and followed by treatment with oral 10 mg/kg corticosteroids for five days...
January 19, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27997281/use-of-compounded-dextromethorphan-quinidine-suspension-for-pseudobulbar-affect-in-hospice-patients
#7
Robert G Wahler, Alfred T Reiman, Joshua V Schrader
BACKGROUND: Pseudobulbar affect (PBA) consists of unprovoked and uncontrollable episodes of laughing and/or crying. In end-of-life situations, PBA symptoms can be especially distressing to family and friends during an already heightened emotional time. Although a commercial product combining dextromethorphan and quinidine (DMQ) is FDA approved for use in PBA, many hospice patients are unable to swallow any solids or semisolids. An alternative formulation for these patients is needed. OBJECTIVE: We present here two cases in which we used a compounded DMQ suspension successfully to treat PBA symptoms in the weeks before the patients' death...
December 20, 2016: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/27978469/highly-sensitive-lc-ms-ms-methods-for-the-determination-of-seven-human-cyp450-activities-using-small-oral-doses-of-probe-drugs-in-human
#8
Alexia Grangeon, Sophie Gravel, Fleur Gaudette, Jacques Turgeon, Veronique Michaud
Cocktails composed of several Cytochrome P450 (CYP450)-selective probe drugs have been shown of value to characterize in vivo drug-metabolism activities. Our objective was to develop and validate highly sensitive and selective LC-MS/MS assays allowing the determination of seven major human CYP450 isoenzyme activities following administration of low oral doses of a modified CYP450 probe-drug cocktail in patients. The seven-drug cocktail was composed of caffeine, bupropion, tolbutamide, omeprazole, dextromethorphan, midazolam (all administered concomitantly) and chlorzoxazone (administered separately) to phenotype for CYP1A2, 2B6, 2C9, 2C19, 2D6, 3A4/5 and 2E1, respectively...
January 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27975343/need-for-better-diabetes-treatment-the-therapeutic-potential-of-nmda-receptor-antagonists
#9
A Welters, E Lammert, E Mayatepek, T Meissner
Diabetes mellitus is the most common metabolic disorder in children and adolescents. Optimal control of blood glucose concentration is essential to prevent acute and diabetic long-term complications. The options to treat diabetes have clearly improved over the last decades, however, to date neither type 1 diabetes nor type 2 diabetes mellitus can be cured. Therefore, diabetes research aims at developing β-cell protective agents that prevent or even reverse diabetes onset. N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are widely expressed in the central nervous system (CNS) where they hold central roles in CNS function...
December 14, 2016: Klinische Pädiatrie
https://www.readbyqxmd.com/read/27941910/effects-of-dextromethorphan-on-mdma-induced-serotonergic-aberration-in-the-brains-of-non-human-primates-using-123-i-adam-spect
#10
Kuo-Hsing Ma, Tsung-Ta Liu, Shao-Ju Weng, Chien-Fu F Chen, Yuahn-Sieh Huang, Sheau-Huei Chueh, Mei-Hsiu Liao, Kang-Wei Chang, Chi-Chang Sung, Te-Hung Hsu, Wen-Sheng Huang, Cheng-Yi Cheng
3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM)...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27936965/avp-786-for-the-treatment-of-agitation-in-dementia-of-the-alzheimer-s-type
#11
Ricardo P Garay, George T Grossberg
Agitation is common and distressing in patients with Alzheimer-type dementia, but safe, effective treatments remain elusive. Psychological treatments are first-line options, but they have limited efficacy. Off-label psychotropic medications are frequently used, but they also have limited effectiveness, and their use may have harmful side effects, including death. Areas covered: This review discusses the history leading to the conception of AVP-786 (deuterated (d6)-dextromethorphan/quinidine), its pharmacokinetic and pharmacodynamic profiles and safety issues, together with an overview of recent clinical trials...
January 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27930497/the-comt-val158met-polymorphism-is-associated-with-response-to-add-on-dextromethorphan-treatment-in-bipolar-disorder
#12
Sheng-Yu Lee, Shiou-Lan Chen, Tzu-Yun Wang, Yun-Hsuan Chang, Po See Chen, San-Yuan Huang, Nian-Sheng Tzeng, Liang-Jen Wang, I Hui Lee, Kao Ching Chen, Yen Kuang Yang, Ru-Band Lu
PURPOSE/BACKGROUND: We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD...
February 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/27910730/retrospective-use-of-pbpk-modelling-to-understand-a-clinical-drug-drug-interaction-between-dextromethorphan-and-gsk1034702
#13
Michael J Hobbs, Jackie Bloomer, Gordon Dear
: 1. PURPOSE: In a clinical trial, a strong drug-drug interaction (DDI) was observed between dextromethorphan (DM, the object or victim drug) and GSK1034702 (the precipitant or perpetrator drug), following single and repeat doses. This study determined the inhibition parameters of GSK1034702 in vitro and applied PBPK modelling approaches to simulate the clinical observations and provide mechanistic hypotheses to understand the DDI. 2. METHODS: In vitro assays were conducted to determine the inhibition parameters of human CYP2D6 by GSK1034702...
December 2, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27908707/the-role-of-nmda-receptor-and-nitric-oxide-cyclic-guanosine-monophosphate-pathway-in-the-antidepressant-like-effect-of-dextromethorphan-in-mice-forced-swimming-test-and-tail-suspension-test
#14
Ehsan Sakhaee, Sattar Ostadhadi, Muhammad Imran Khan, Farbod Yousefi, Abbas Norouzi-Javidan, Reyhaneh Akbarian, Mohsen Chamanara, Samira Zolfaghari, Ahmad-Reza Dehpour
Depression is a devastating disorder which has a high impact on the wellbeing of overall society. As such, need for innovative therapeutic agents are always there. Most of the researchers focused on N-methyl-d-aspartate receptor to explore the antidepressant like activity of new therapeutic agents. Dextromethorphan is a cough suppressant agent with potential antidepressant activity reported in mouse force swimming test. Considering N-methyl-d-aspartate as a forefront in exploring antidepressant agents, here we focused to unpin the antidepressant mechanism of dextromethorphan targeting N-methyl-d-aspartate receptor induced nitric oxide-cyclic guanosine monophosphate signaling...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27886853/airway-remodeling-associated-with-cough-hypersensitivity-as-a-consequence-of-persistent-cough-an-experimental-study
#15
Hitoshi Nakaji, Akio Niimi, Hirofumi Matsuoka, Toshiyuki Iwata, Shilei Cui, Hisako Matsumoto, Isao Ito, Tsuyoshi Oguma, Kojiro Otsuka, Tomoshi Takeda, Hideki Inoue, Tomoko Tajiri, Tadao Nagasaki, Yoshihiro Kanemitsu, Kazuo Chin, Michiaki Mishima
BACKGROUND: Chronic cough involves airway remodeling associated with cough reflex hypersensitivity. Whether cough itself induces these features remains unknown. METHODS: Guinea pigs were assigned to receive treatment with citric acid (CA), saline (SA), or CA+dextromethorphan (DEX). All animals were exposed to 0.5M CA on days 1 and 22. On days 4-20, the CA and CA+DEX groups were exposed to CA, and the SA group to saline thrice weekly, during which the CA+DEX group was administered DEX pretreatment to inhibit cough...
November 2016: Respiratory Investigation
https://www.readbyqxmd.com/read/27867308/effect-of-n-methyl-d-aspartate-receptor-antagonist-dextromethorphan-on-opioid-analgesia-in-pediatric-intensive-care-unit
#16
Mohammed Naeem, Hala Al Alem, Ali Al Shehri, Majed Al-Jeraisy
Objective. Pain control is an essential goal in the management of critical children. Narcotics are the mainstay for pain control. Patients frequently need escalating doses of narcotics. In such cases an adjunctive therapy may be beneficial. Dextromethorphan (DM) is NMDA receptor antagonist and may prevent tolerance to narcotics; however, its definitive role is still unclear. We sought whether dextromethorphan addition could decrease the requirements of fentanyl to control pain in critical children. Design. Double-blind, randomized control trial (RCT)...
2016: Pain Research & Management: the Journal of the Canadian Pain Society
https://www.readbyqxmd.com/read/27867000/neuromodulatory-effects-of-the-dorsal-hippocampal-endocannabinoid-system-in-dextromethorphan-morphine-induced-amnesia
#17
Zahra Ghasemzadeh, Ameneh Rezayof
Dextromethorphan which is an active ingredient in many cough medicines has been previously shown to potentiate amnesic effect of morphine in rats. However, the effect of dextromethorphan, that is also a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in combination with morphine on hippocampus-based long term memory has not been well characterized. The aim of the present study was to assess the possible role of endocannabinoid system of the dorsal hippocampus in dextromethorphan /morphine-induced amnesia...
January 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27855728/dextromethorphan-quinidine-responsive-pseudobulbar-affect-pba-psychopharmacological-model-for-wide-ranging-disorders-of-emotional-expression
#18
Stephen M Stahl
The symptoms of emotional dysregulation associated with the syndrome known as pseudobulbar affect (PBA) can be effectively treated by the sigma, glutamate, and serotonergic agent dextromethorphan combined with quinidine. If the same brain circuits affected in PBA are also compromised in related disorders of emotional expression, dextromethorphan-quinidine and other novel sigma-glutamate-serotonin agents could prove to be novel psychopharmacologic treatments for these conditions as well.
December 2016: CNS Spectrums
https://www.readbyqxmd.com/read/27849505/a-prospective-observation-study-of-medical-toxicology-consultation-in-a-u-s-combat-theater
#19
Joseph K Maddry, Patrick C Ng, Daniel Sessions, Vikhyat S Bebarta
OBJECTIVES: Since 2001, U.S. military personnel and active duty, uniformed physicians providing medical support have been deployed to Afghanistan. Medical toxicologists are among the physicians deployed. There is a paucity of information present in the literature that has documented cases treated by toxicologists in theater. This prospective observational study describes 15 male patients treated in theater by a military medical toxicologist. METHODS: We performed a prospective observational study in which a medical toxicologist consulted and reported on deployed toxicology cases occurring during a 5-month deployment to Bagram, Afghanistan...
November 2016: Military Medicine
https://www.readbyqxmd.com/read/27843771/multi-modal-preemptive-analgesia-with-pregabalin-acetaminophen-naproxen-and-dextromethorphan-in-radical-neck-dissection-surgery-a-randomized-clinical-trial
#20
Hamid Reza Amiri, Mojtaba Mirzaei, Mohammad Taghi Beig Mohammadi, Farhad Tavakoli
BACKGROUND: Preemptive analgesia may be considered as a method not only to alleviate postoperative pain but also to decrease analgesic consumption. Different regimens are suggested, but there is currently no standard. OBJECTIVES: The aim was to measure the efficacy of preemptive analgesia with pregabalin, acetaminophen, naproxen, and dextromethorphan in radical neck dissection surgery for reducing the intensity of pain and morphine consumption. PATIENTS AND METHODS: This study was conducted as a randomized double-blind clinical trial...
August 2016: Anesthesiology and Pain Medicine
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