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Dextromethorphan

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https://www.readbyqxmd.com/read/28936010/dextromethorphan-in-cough-syrup-the-poor-man-s-psychosis
#1
Bridgette Martinak, Ramy A Bolis, Jeffrey Ryne Black, Rachel E Fargason, Badari Birur
Dextromethorphan (3-methoxy-N-methylmorphinan), also known as "DXM" and "the poor man's PCP," is a synthetically produced drug that is available in more than 140 over-the-counter cough and cold preparations. Dextromethorphan (DXM) has overtaken codeine as the most widely used cough suppressant due to its availability, efficacy, and safety profile at directed doses. However, DXM is subject to abuse. When consumed at inappropriately high doses (over 1500 mg/day), DXM can induce a state of psychosis characterized by Phencyclidine (PCP)-like psychological symptoms, including delusions, hallucinations, and paranoia...
September 15, 2017: Psychopharmacology Bulletin
https://www.readbyqxmd.com/read/28935657/use-of-hybrid-capillary-tube-setup-on-400mhz-nmr-for-quantitation-of-crucial-low-quantity-metabolites-using-asicco-signal
#2
Ranjeet Tiwari, Deepak Ahire, Hemantha Kumar, Sarmistha Sinha, Siddheshwar Kisan Chauthe, Murali Subramanian, Ramaswamy Iyer, Ramakanth Sarabu, Lakshmi Kant Bajpai
Metabolites of new chemical entities can influence safety and efficacy of a molecule and often times need to be quantified in preclinical studies. However, synthetic standards of metabolites are very rarely available in early discovery. Alternate approaches such as bio-synthesis needs to be explored to generate these metabolites. Assessing the quantity and purity of these small amounts of metabolites with a non-destructive analytical procedure becomes crucial. Quantitative nuclear magnetic resonance (qNMR) becomes the method of choice for these samples...
September 21, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28931647/randomized-open-label-trial-of-dextromethorphan-in-rett-syndrome
#3
Constance L Smith-Hicks, Siddharth Gupta, Joshua B Ewen, Manisha Hong, Lisa Kratz, Richard Kelley, Elaine Tierney, Rebecca Vaurio, Genila Bibat, Abanti Sanyal, Gayane Yenokyan, Nga Brereton, Michael V Johnston, Sakkubai Naidu
OBJECTIVE: To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. METHODS: We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting...
September 20, 2017: Neurology
https://www.readbyqxmd.com/read/28925030/drug-repurposing-may-generate-novel-approaches-to-treating-depression
#4
REVIEW
Mohamed Elsaed Ebada
OBJECTIVES: The breakthrough advancements in scientific medical research have greatly improved our understanding of the pathogenesis of depression, encouraging drug discoverers to take a shorter path than ever through drug repurposing to generate new antidepressant medications. In addition to reduced noradrenergic and serotonergic neurotransmission in the brain, other coincidence features such as glutamate neurotoxicity, inflammation and/or cerebrovascular insufficiency are implicated in the pathogenesis of major depressive disorder and late-life depression...
September 18, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28916283/deuterated-d6-dextromethorphan-elicits-antidepressant-like-effects-in-mice
#5
Linda Nguyen, Anna L Scandinaro, Rae R Matsumoto
The over-the-counter antitussive dextromethorphan (DM) may have rapid antidepressant actions based on its overlapping pharmacology with ketamine, which has shown fast antidepressant effects but whose widespread use remains limited by problematic side effects. We have previously shown that DM produces antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST) that are mediated in part through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic (AMPA) and sigma-1 receptors, two protein targets associated with a faster onset of antidepressant efficacy...
September 12, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28916251/mk-801-but-not-naloxone-attenuates-high-dose-dextromethorphan-induced-convulsive-behavior-possible-involvement-of-the-glun2b-receptor
#6
Hai-Quyen Tran, Yoon Hee Chung, Eun-Joo Shin, The-Vinh Tran, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung-Chun Kim
Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity...
September 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28900117/dextromethorphan-exhibits-anti-inflammatory-and-immunomodulatory-effects-in-a-murine-model-of-collagen-induced-arthritis-and-in-human-rheumatoid-arthritis
#7
Der-Yuan Chen, Chi-Chien Lin, Yi-Ming Chen, Ya-Hsuan Chao, Deng-Ho Yang
Dextromethorphan (d-3-methoxy-17-methylmorphinan, DXM) is a commonly used antitussive with a favorable safety profile. Previous studies have demonstrated that DXM has anti-inflammatory and immunomodulatory properties; however, the effect of DXM in rheumatoid arthritis (RA) remains unknown. Herein, we found that DXM treatment attenuated arthritis severity and proinflammatory cytokine expression levels, including TNF-α, IL-6, and IL-17A, in paw tissues of CIA mice. DXM treatment also reduced serum TNF-α, IL-6, and IL-17A levels of CIA mice and patients with RA...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28891835/the-effect-of-dextromethorphan-premedication-on-cough-and-patient-tolerance-during-flexible-bronchoscopy-a-randomized-double-blind-placebo-controlled-trial
#8
Shahideh Amini, Soheil Peiman, Mahdi Khatuni, Marziyeh Ghalamkari, Besharat Rahimi
BACKGROUND: Patients undergoing bronchoscopy can experience problems such as anxiety and cough, requiring various doses of sedatives and analgesics. The purposes of this study were to investigate the effect of premedication with dextromethorphan on patients' cough and anxiety, and the use of analgesics/sedatives during flexible bronchoscopy (FB). METHODS: A randomized, double-blind, placebo-controlled, prospective study was performed to assess the effect of dextromethorphan premedication on patients who underwent diagnostic bronchoscopy...
September 7, 2017: Journal of Bronchology & Interventional Pulmonology
https://www.readbyqxmd.com/read/28891561/online-monitoring-of-hepatic-rat-metabolism-by-coupling-a-liver-biochip-and-a-mass-spectrometer
#9
Franck Merlier, Rachid Jellali, Eric Leclerc
A microfluidic liver biochip was coupled with a mass spectrometer to detect in real time the drug metabolism of hepatocytes. The hepatocytes were cultivated in the biochip for 35 h. The biochip was placed in a small-scale incubator in which the temperature and CO2 concentration were controlled. The biochip was connected serially to a mass spectrometer, a peristaltic pump and a culture medium reservoir. The injection in the mass spectrometer was performed every 10 min for 11 h. The metabolism of midazolam, phenacetin, omeprazole, dextromethorphan, repaglinide, rosuvastatin, tolbutamide and caffeine was investigated...
September 11, 2017: Analyst
https://www.readbyqxmd.com/read/28877137/a-systematic-review-of-nmda-receptor-antagonists-for-treatment-of-neuropathic-pain-in-clinical-practice
#10
Rohit Aiyer, Neel Mehta, Semih Gungor, Amitabh Gulati
OBJECTIVE: To investigate the efficacy of N-methyl-D-aspartate receptor (NMDA) receptor antagonists for neuropathic pain and review literature to determine if specific pharmacologic agents provide adequate neuropathic pain relief. METHODS: Literature was reviewed on PubMed using a variety of key words for 8 NMDA receptor antagonists. These key words include: "Ketamine and Neuropathy", "Ketamine and Neuropathic Pain", "Methadone and Neuropathy", "Methadone and Neuropathic Pain", "Memantine and Neuropathic pain", "Memantine and Neuropathy", "Amantadine and Neuropathic Pain", "Amantadine and Neuropathy", "Dextromethorphan and Neuropathic Pain", "Dextromethorphan and Neuropathy", "Carbamazepine and Neuropathic Pain", "Carbamazepine and Neuropathy", "Valproic Acid and Neuropathy", "Valproic Acid and Neuropathic Pain", "Phenytoin and Neuropathy" and "Phenytoin and Neuropathic Pain"...
September 1, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28867701/a-metabolic-study-on-the-biochemical-effects-of-chiral-illegal-drugs-in-rats-using-1-h-nmr-spectroscopy
#11
Kiyoshi Fukuhara, Akiko Ohno, Ruri Kikura-Hanajiri
 Considering the pharmacological effects of chiral drugs, enantiopure drugs may differ from their racemic mixture formulation in efficacy, potency, or adverse effects. Levomethorphan (LVM) and Dextromethorphan (DXM) act on the central nervous system and exhibit different pharmacological features. LVM, the l-stereoisomer of methorphan, shows many similarities to opiates such as heroin, morphine and codeine, including the potential for addiction, while the d-stereoisomer, DXM, does not have the same opioid effect...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28830117/analysis-of-dextromethorphan-and-dextrorphan-in-skeletal-remains-following-differential-microclimate-exposure-comparison-of-acute-vs-repeated-drug-exposure
#12
Lucas M Morrison, Kirk A Unger, James H Watterson
Analysis of dextromethorphan (DXM) and its metabolite dextrorphan (DXT) in skeletal remains of rats following acute (ACU, 75 mg/kg, IP, n = 10) or three repeated (REP, 25 mg/kg, IP, n = 10, 40-min interval) doses of DXM is described. Following dosing and euthanasia, rats decomposed outdoors to skeleton in two different microclimate environments (n = 5 ACU and n = 5 REP at each site): Site A (shaded forest microenvironment) and Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Two drug-free rats at each site served as negative controls...
July 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28808886/assessment-of-pharmacokinetic-interactions-between-obeticholic-acid-and-caffeine-midazolam-warfarin-dextromethorphan-omeprazole-rosuvastatin-and-digoxin-in-phase-1-studies-in-healthy-subjects
#13
Jeffrey E Edwards, Lise Eliot, Andrew Parkinson, Sharon Karan, Leigh MacConell
INTRODUCTION: Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. METHODS: Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin)...
August 14, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28807457/identification-of-pseudobulbar-affect-symptoms-in-the-nursing-home-setting-development-and-assessment-of-a-screening-tool
#14
Carrie Allen, Barbara Zarowitz, Terrence O'Shea, Edward Peterson, Charles Yonan, Fanta Waterman
Pseudobulbar Affect (PBA) is a neurologic condition characterized by involuntary outbursts of crying and/or laughing disproportionate to patient mood or social context. Although an estimated 9% of nursing home residents have symptoms suggestive of PBA, they are not routinely screened. Our goal was to develop an electronic screening tool based upon characteristics common to nursing home residents with PBA identified through medical record data. Nursing home residents with PBA treated with dextromethorphan hydrobromide/quinidine sulfate (n = 140) were compared to age-, gender-, and dementia-diagnosis-matched controls without PBA or treatment (n = 140)...
August 11, 2017: Geriatric Nursing
https://www.readbyqxmd.com/read/28756727/effects-of-m-nisoldipine-on-the-activity-and-mrna-expression-of-four-cyp-isozymes-in-rats
#15
Yupeng Sun, Yanyan Liu, Xia Zhang, Changchen Wan, Tao Lyu, Lantong Zhang
1. For the first time, a systemic in vivo investigation was employed to evaluate the potential effects of m-nisoldipine on activities of rat cytochrome P450 enzymes (CYP1A2, CYP2C11, CYP2D1 and CYP3A1) by both cocktail probe drugs and the quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR). 2. m-Nisoldipine-treated and blank control groups were respectively administered m-nisoldipine at the dosage of 2.5, 5 and 12.5 mg/kg and CMC-Na solution for 15 days consecutively, then they were given the probe drugs of caffeine, diclofenac, dextromethorphan and midazolam (all probes were 5 mg/kg) by p...
July 31, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28739134/nmda-receptor-modulation-by-dextromethorphan-and-acute-stress-selectively-alters-electroencephalographic-indicators-of-partial-report-processing
#16
Lisa J Weckesser, Sören Enge, Philipp Riedel, Clemens Kirschbaum, Robert Miller
Proceeding from a biophysical network model, the present study hypothesized that glutamatergic neurotransmission across the NMDA receptor (NMDAR) plays a key role in visual perception and its modulation by acute stress. To investigate these hypotheses, behavioral and electroencephalographic (EEG) indicators of partial report task processing were assessed in twenty-four healthy young men who randomly received a non-competitive NMDAR antagonist (0.8 mg/kg dextromethorphan, DXM) or a placebo, and concurrently accomplished a stress-induction (MAST) or control protocol in three consecutive sessions...
July 21, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28699480/adulteration-practices-of-psychoactive-illicit-drugs-an-updated-review
#17
Renata Solimini, Maria Concetta Rotolo, Manuela Pellegrini, Adele Minutillo, Roberta Pacifici, Francesco Paolo Busardò, Simona Zaami
BACKGROUND: It is well known that powdery drugs such as cocaine and heroin are frequently adulterated or diluted predominantly to obtain more doses and to increase the drug dealer's profits, but also to enhance, to modify or to oppose drug effects. METHODS: The aim of this report is to provide an overview of the recent scientific literature on medicines as well as on new psychoactive substances, used as cutting agents (i.e. pharmacologically active adulterants) and on the related adverse health effects on consumers, possibly due to the synergistic effect of the adulterants laced with substances of abuse, which represent a matter of great concern because of the frequent fatalities...
July 10, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28691510/treatment-of-pseudobulbar-affect-with-fluoxetine-and-dextromethorphan-in-a-woman-with-multiple-sclerosis
#18
Ian McGrane, Amy VandenBerg, Robert Munjal
No abstract text is available yet for this article.
July 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28679672/the-impact-of-the-hepatocyte-to-plasma-ph-gradient-on-the-prediction-of-hepatic-clearance-and-drug-drug-interactions-for-cyp2c9-and-cyp3a4-substrates
#19
Luc Raymond Albert Rougee, Michael A Mohutsky, David W Bedwell, Kenneth J Ruterbories, Stephen D Hall
Surrogate assays for drug metabolism and inhibition are traditionally performed in buffer systems at pH 7.4, despite evidence that hepatocyte intracellular pH is 7.0. This pH gradient can result in a pKa-dependent change in intracellular/extracellular concentrations for ionizable drugs that could affect predictions of clearance and P450 inhibition. The effect of microsomal incubation pH on in vitro enzyme kinetic parameters for CYP2C9 (diclofenac, (S)-warfarin) and CYP3A4 (midazolam, dextromethorphan, testosterone) substrates, enzyme specific reversible inhibitors (amiodarone, desethylamiodarone, clozapine, nicardipine, fluconazole, fluvoxamine, itraconazole) and a mechanism-based inhibitor (amiodarone) was investigated...
July 5, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28655493/eeg-with-extreme-delta-brush-in-young-female-with-methotrexate-neurotoxicity-supports-nmda-receptor-involvement
#20
Lisbeth Samsø Schmidt, Troels W Kjær, Kjeld Schmiegelow, Alfred Peter Born
Sub-acute neurotoxicity is a well-known complication to high-dose and intrathecal methotrexate (MTX) treatment of children with leukemia. Symptoms can be treated safely by dextromethorphan, a non-competitive antagonist to N-methyl-D-aspartic acid receptor (NMDAR). In a female with subacute MTX neurotoxicity, we observed an electroencephalographic (EEG) with extreme delta brush. Extreme delta brush is an EEG pattern previously described in patients with NMDAR autoimmune encephalitis. The observations suggest that the mechanism of this neurotoxicity may be mediated by the NMDAR...
September 2017: European Journal of Paediatric Neurology: EJPN
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