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Drug induced neurotoxicity

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https://www.readbyqxmd.com/read/29434546/matrine-is-identified-as-a-novel-macropinocytosis-inducer-by-a-network-target-approach
#1
Bo Zhang, Xin Wang, Yan Li, Min Wu, Shu-Yan Wang, Shao Li
Comprehensively understanding pharmacological functions of natural products is a key issue to be addressed for the discovery of new drugs. Unlike some single-target drugs, natural products always exert diverse therapeutic effects through acting on a "network" that consists of multiple targets, making it necessary to develop a systematic approach, e.g., network pharmacology, to reveal pharmacological functions of natural products and infer their mechanisms of action. In this work, to identify the "network target" of a natural product, we perform a functional analysis of matrine, a marketed drug in China extracted from a medical herb Ku-Shen (Radix Sophorae Flavescentis)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29434381/ismp-adverse-drug-reactions-influenza-vaccine-induced-stevens-johnson-syndrome-vilazodone-induced-nightmares-dabigatran-induced-pustular-eruptions-neurotoxic-and-cardiotoxic-symptoms-after-cannabis-concentrate-exposure-rosuvastatin-induced-skin-eruption
#2
Michael A Mancano
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested...
February 2018: Hospital Pharmacy
https://www.readbyqxmd.com/read/29433392/the-protective-effects-of-gardenia-jasminoides-fructus-gardenia-on-amyloid-%C3%AE-induced-mouse-cognitive-impairment-and-neurotoxicity
#3
Cai-Xia Zang, Xiu-Qi Bao, Lin Li, Han-Yu Yang, Lu Wang, Yang Yu, Xiao-Liang Wang, Xin-Sheng Yao, Dan Zhang
Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. Although the exact causes of AD have not yet been fully elucidated, cholinergic dysfunction, mitochondrial damage, oxidative stress and neuroinflammation have been recognized as influential factors. Current drugs that are designed to address only a single target are unable to mitigate or prevent the progression of this complicated disease, so new disease-modifying drugs are urgently needed. Chinese herbs with thousand years of effective usage might be a good source for potential drugs...
February 12, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29432676/genistein-a-dual-inhibitor-of-both-a%C3%AE-and-hiapp-peptides
#4
Baiping Ren, Yonglan Liu, Yanxian Zhang, Yongqing Cai, Xiong Gong, Yung Chang, Lijian Xu, Jie Zheng
Abnormal misfolding and aggregation of amyloid peptides into amyloid fibrils are a common and critical pathological event in many neurodegenerative diseases. Most of inhibitors or drugs have been developed to prevent amyloid aggregation of a specific peptide, exhibiting sequence-dependent inhibition mechanisms. It is more challenging to develop or discover inhibitors capable of preventing the aggregation of two or more different amyloid peptides. Genistein, a major phytoestrogen in soybean, has been widely used as anti-inflammation and cerebrovascular drugs due to their anti-oxidation and anti-acetylcholinesterase effects...
February 12, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29432603/in-vitro-screening-for-seizure-liability-using-microelectrode-array-technology
#5
Jenifer A Bradley, Harry H Luithardt, Monica R Metea, Christopher J Strock
Drug induced seizure liabilities produce significant compound attrition during drug discovery. Currently available in vitro cytotoxicity assays cannot predict all toxicity mechanisms due to the failure of these assays to predict sublethal target specific electrophysiological liabilities. Identification of seizurogenic and other electrophysiological effects at early stages of the drug development process is important to ensure that safe candidate compounds can be developed while chemical design is taking place, long before these liabilities are discovered in costly preclinical in vivo studies...
February 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29430172/dysregulation-of-neuregulin-1-erbb-signaling-in-the-hippocampus-of-rats-after-administration-of-doxorubicin
#6
Dehua Liao, Yujin Guo, Daxiong Xiang, Ruili Dang, Pengfei Xu, Hualin Cai, Lizhi Cao, Pei Jiang
Objective: Long-term use of doxorubicin (Dox) can cause neurobiological side effects associated with depression, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in neural function, much is still unknown concerning the biological link between the NRG1/ErbB pathway and the Dox-induced neurotoxicity. Therefore, we examined the protein expression of NRG1 and ErbB receptors in the hippocampus of rats following Dox treatment...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29427706/in-vitro-assessment-of-chemotherapy-induced-neuronal-toxicity
#7
Chelsea Snyder, Lanlan Yu, Tin Ngo, Daniel Sheinson, Yuda Zhu, Min Tseng, Dinah Misner, Karin Staflin
Neurotoxicity is a major concern during drug development, and together with liver and cardio-toxicity, it is one of the main causes of clinical drug attrition. Current pre-clinical models may not sufficiently identify and predict the risk for central or peripheral nervous system toxicity. One such example is clinically dose-limiting neuropathic effects after the administration of chemotherapeutic agents. Thus, the need to establish novel in vitro tools to evaluate the risk of neurotoxicities, such as neuropathy, remains unmet in drug discovery...
February 7, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29427284/a-single-high-dose-of-methamphetamine-reduces-monoamines-and-impairs-egocentric-and-allocentric-learning-and-memory-in-adult-male-rats
#8
Arnold Gutierrez, Michael T Williams, Charles V Vorhees
Methamphetamine (MA) alters dopamine markers and cognitive function in heavy users. In rodents, there are MA dosing regimens that induce concordant effects using repeated administration at spaced intervals. These regimens are effective but complicate experiments designed to disentangle the effects of the drug on different brain regions in relation to their cognitive effects because of treatment spacing. In an effort to simplify the model, we tested whether a single dose of MA could induce the same monoamine and cognitive effects as multiple, spaced dosing without affecting survival...
February 9, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29386447/-underlying-mechanisms-of-methamphetamine-induced-self-injurious-behavior-and-lethal-effects-in-mice
#9
Tomohisa Mori, Toshiko Sawaguchi
Relatively high doses of psychostimulants induce neurotoxicity on the dopaminergic system and self-injurious behavior (SIB) in rodents. However the underlying neuronal mechanisms of SIB remains unclear. Dopamine receptor antagonists, N-methyl-D-aspartic acid (NMDA) receptor antagonists, Nitric Oxide Synthase (NOS) inhibitors and free radical scavengers significantly attenuate methamphetamine-induced SIB. These findings indicate that activation of dopamine as well as NMDA receptors followed by radical formation and oxidative stress, especially when mediated by NOS activation, is associated with methamphetamine-induced SIB...
2018: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
https://www.readbyqxmd.com/read/29377288/effects-of-anti-inflammatory-drugs-on-the-expression-of-tryptophan-metabolism-genes-by-human-macrophages
#10
Tim Regan, Andrew C Gill, Sara M Clohisey, Mark W Barnett, Carmine M Pariante, Neil A Harrison, David A Hume, Edward T Bullmore, Tom C Freeman
Several lines of evidence link macrophage activation and inflammation with (monoaminergic) nervous systems in the etiology of depression. IFN treatment is associated with depressive symptoms, whereas anti-TNFα therapies elicit positive mood. This study describes the actions of 2 monoaminergic antidepressants (escitalopram, nortriptyline) and 3 anti-inflammatory drugs (indomethacin, prednisolone, and anti-TNFα antibody) on the response of human monocyte-derived macrophages (MDMs) from 6 individuals to LPS or IFN-α...
January 26, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29377255/agmatine-co-treatment-attenuates-allodynia-and-structural-abnormalities-in-cisplatin-induced-neuropathy-in-rats
#11
Basak Donertas, Cigdem Cengelli Unel, Sule Aydin, Emel Ulupinar, Orhan Ozatik, Bilgin Kaygisiz, Engin Yildirim, Kevser Erol
Cisplatin is a widely-used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin-induced neurotoxicity...
January 29, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29369918/public-health-impact-of-androgens
#12
Gen Kanayama, Marc J Kaufman, Harrison G Pope
PURPOSE OF REVIEW: To summarize recent findings regarding the public health impact of androgen abuse. RECENT FINDINGS: Abuse of androgens (also called 'anabolic-androgenic steroids') has grown into a major worldwide substance abuse problem involving tens of millions of individuals, of whom about 98% are men. Most androgen abusers are still under age 50 today, and thus, the long-term effects of these drugs are only beginning to be understood. Recent studies confirm that long-term supraphysiologic androgen exposure produces cardiovascular toxicity, characterized especially by cardiomyopathy and atherosclerotic disease...
January 24, 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/29366690/comparative-neurotoxicity-study-of-mercury-based-inorganic-compounds-including-ayurvedic-medicines-rasasindura-and-kajjali-in-zebrafish-model
#13
Snehasis Biswas, Naay Balodia, Jayesh Bellare
Zebrafish behavioral model is a powerful tool for neuroscience research. Behavioral changes in the zebrafish are studied by administering drugs. With the aid of automated and open-source MATLAB program, high-accuracy tracking of zebrafish can be achieved, and the important behavioral parameters can be calculated. Although mercury is accepted as a potent neurotoxin, used as a key element for preparing certain Ayurvedic medicines. In this work, mercury-based inorganic compounds, including HgCl2, HgS, and Ayurvedic medicines (Rasasindura and Kajjali) were administrated in zebrafish, and the effects on various behavioral parameters and cortisol levels were studied...
January 20, 2018: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29366689/in-vivo-study-of-teratogenic-and-anticonvulsant-effects-of-antiepileptics-drugs-in-zebrafish-embryo-and-larvae
#14
C S Martinez, D A Feas, M Siri, D E Igartúa, N S Chiaramoni, SdV Alonso, M J Prieto
Epilepsy is a neurological disorder treated with antiepileptic drugs (AEDs). Since AEDs are administered in women in childbearing age, it is critical to study if drugs are capable of inducing developmental toxicity. Along the bibliography available, there is no research comparing teratogenicity and anticonvulsant effect within the same study. In the present study, we evaluated the teratogenic and anticonvulsant effects of six different AEDs: carbamazepine, levetiracetam, lamotrigine, phenobarbital, phenytoin and valproic acid...
January 20, 2018: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29357878/unconjugated-bilirubin-induces-pyroptosis-in-cultured-rat-cortical-astrocytes
#15
Jie Feng, Mengwen Li, Qian Wei, Shengjun Li, Sijie Song, Ziyu Hua
BACKGROUND: Bilirubin-induced neurological dysfunction (BIND), a severe complication of extreme neonatal hyperbilirubinemia, could develop into permanent neurodevelopmental impairments. Several studies have demonstrated that inflammation and nerve cell death play important roles in bilirubin-induced neurotoxicity; however, the underlying mechanism remains unidentified. METHODS: The present study was intended to investigate whether pyroptosis, a highly inflammatory form of programmed cell death, participated in the bilirubin-mediated toxicity on cultured rat cortical astrocytes...
January 22, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29344837/evaluation-of-the-profile-and-mechanism-of-neurotoxicity-of-water-soluble-cu-p-4-pf6-and-au-p-4-pf6-p-thp-or-pta-anticancer-complexes
#16
C Ceresa, G Nicolini, S Semperboni, V Gandin, M Monfrini, F Avezza, P Alberti, A Bravin, M Pellei, C Santini, Guido Cavaletti
[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For these reasons, they have been proposed as a valid alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based compounds were not neurotoxic even at concentrations higher than the IC50 obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 in cancer cell lines...
January 17, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29337310/oatp1b2-deficiency-protects-against-paclitaxel-induced-neurotoxicity
#17
Alix F Leblanc, Jason A Sprowl, Paola Alberti, Alessia Chiorazzi, W David Arnold, Alice A Gibson, Kristen W Hong, Marissa S Pioso, Mingqing Chen, Kevin M Huang, Vamsi Chodisetty, Olivia Costa, Tatiana Florea, Peter de Bruijn, Ron H Mathijssen, Raquel E Reinbolt, Maryam B Lustberg, Lara E Sucheston-Campbell, Guido Cavaletti, Alex Sparreboom, Shuiying Hu
Paclitaxel is among the most widely used anticancer drugs and is known to cause a dose-limiting peripheral neurotoxicity, the initiating mechanisms of which remain unknown. Here, we identified the murine solute carrier organic anion-transporting polypeptide B2 (OATP1B2) as a mediator of paclitaxel-induced neurotoxicity. Additionally, using established tests to assess acute and chronic paclitaxel-induced neurotoxicity, we found that genetic or pharmacologic knockout of OATP1B2 protected mice from mechanically induced allodynia, thermal hyperalgesia, and changes in digital maximal action potential amplitudes...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29336266/design-synthesis-evaluation-and-computational-studies-of-nipecotic-acid-acetonaphthone-hybrids-as-potential-antiepileptic-agents
#18
Ankit Seth, Piyoosh A Sharma, Avanish Tripathi, Priyanka K Choubey, Pavan Srivastava, Prabhash N Tripathi, Sushant Kumar Shrivastava
BACKGROUND: Nipecotic acid is considered to be one of the most potent inhibitors of neuronal and glial γ- aminobutyric acid (GABA) uptake in vitro. However nipecotic acid does not readily cross the blood-brain barrier (BBB) following peripheral administration, owing to its hydrophilic nature. OBJECTIVE: A series of substituted acetonaphthones tethered nipecotic acid derivatives were designed and synthesized with an aim to improve the lipophilicity and the blood-brain barrier (BBB) permeation...
January 15, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29331789/anticonvulsant-activities-of-%C3%AE-asaronol-e-3-hydroxyasarone-an-active-constituent-derived-from-%C3%AE-asarone
#19
Xirui He, Yajun Bai, Min Zeng, Zefeng Zhao, Qiang Zhang, Ning Xu, Fanggang Qin, Xiaoyang Wei, Meimei Zhao, Ni Wu, Zehua Li, Yajun Zhang, Tai-Ping Fan, Xiaohui Zheng
BACKGROUND: Epilepsy is one of chronic neurological disorders that affects 0.5-1.0% of the world's population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile. METHODS: α-Asaronol and two current antiseizure drugs (α-asarone and carbamazepine (CBZ)) were assessed by in vivo anticonvulsant screening with the three most employed standard animal seizure models, including maximal electroshock seizure (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3-mercaptopropionic acid (3-MP)-induced seizures in mice...
August 31, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29318511/midazolam-efficacy-against-acute-hydrogen-sulfide-induced-mortality-and-neurotoxicity
#20
Poojya Anantharam, Dong-Suk Kim, Elizabeth M Whitley, Belinda Mahama, Paula Imerman, Piyush Padhi, Wilson K Rumbeiha
Hydrogen sulfide (H2S) is a colorless, highly neurotoxic gas. It is not only an occupational and environmental hazard but also of concern to the Department of Homeland Security for potential nefarious use. Acute high-dose H2S exposure causes death, while survivors may develop neurological sequelae. Currently, there is no suitable antidote for treatment of acute H2S-induced neurotoxicity. Midazolam (MDZ), an anti-convulsant drug recommended for treatment of nerve agent intoxications, could also be of value in treating acute H2S intoxication...
January 9, 2018: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
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