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Drug induced neurotoxicity

Mariana Angoa-Pérez, John H Anneken, Donald M Kuhn
The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties...
October 18, 2016: Current Topics in Behavioral Neurosciences
Asad Jan, Brandon Jansonius, Alberto Delaidelli, Syam Prakash Somasekharan, Forum Bhanshali, Milène Vandal, Gian Luca Negri, Don Moerman, Ian MacKenzie, Frédéric Calon, Michael R Hayden, Stefan Taubert, Poul H Sorensen
Soluble oligomers of amyloid-β (Aβ) impair synaptic plasticity, perturb neuronal energy homeostasis, and are implicated in Alzheimer's disease (AD) pathogenesis. Therefore, significant efforts in AD drug discovery research aim to prevent the formation of Aβ oligomers or block their neurotoxicity. The eukaryotic elongation factor-2 kinase (eEF2K) plays a critical role in synaptic plasticity, and couples neurotransmission to local dendritic mRNA translation. Recent evidence indicates that Aβ oligomers activate neuronal eEF2K, suggesting a potential link to Aβ induced synaptic dysfunction...
October 17, 2016: Acta Neuropathologica
Laszlo Vutskits, Zhongcong Xie
General anaesthesia is usually considered to safely induce a reversible brain state allowing the performance of surgery under optimal conditions. An increasing number of clinical and experimental observations, however, suggest that anaesthetic drugs, especially when they are administered at the extremes of age, can trigger long-term morphological and functional alterations in the brain. Here, we review available mechanistic data linking general-anaesthesia exposure to impaired cognitive performance in both young and mature nervous systems...
October 18, 2016: Nature Reviews. Neuroscience
Pil Sung Gu, Minho Moon, Jin Gyu Choi, Myung Sook Oh
Mulberry fruit, which has been long used in traditional oriental medicine, was reported to ameliorate motor dysfunction and dopaminergic neuronal degeneration via antioxidant and antiapoptotic effects in an animal model of Parkinson's disease (PD). More than 95% of PD patients exhibit nonmotor problems such as olfactory dysfunction and gastrointestinal constipation, which are generally considered to be early symptoms of PD. However, few studies have actually examined potential drugs to treat early PD symptoms...
September 22, 2016: Journal of Nutritional Biochemistry
Pia Basaure, Fiona Peris-Sampedro, Maria Cabré, Ingrid Reverte, Maria Teresa Colomina
Cholinesterases (ChE) are common targets of organophosphate (OP) pesticides and play a critical role in the pathology of some dementias. While chlorpyrifos (CPF) remains one of the most commonly used OPs in the world, numerous investigations have reported its neurotoxic potential and highlighted behavioral disturbances upon its administration. Rivastigmine currently serves to treat Alzheimer's disease, but it may induce cholinergic overstimulation in non-demented individuals. The present investigation aimed to compare the acute and delayed effects caused by both ChE inhibitors in adult C57BL/6 male mice...
October 9, 2016: Behavioural Brain Research
Yo Shinoda, Yui Nakajima, Hirotoshi Iguchi, Satoshi Tatsumi, Motomitsu Kitaoka, Masahiro Nakajima, Tsutomu Takahashi, Yasuyuki Fujiwara, Teiichi Furuichi
Galacto-N-biose (GNB: Galβ1-3GalNAc) is an O-glycan disaccharide core moiety that is a core component of mucin in the gastrointestinal tract; however, the physiological properties of GNB are not well understood. Glutamate excitotoxicity causes neuronal death in acute neurological disorders including stroke, trauma, and neurodegenerative disease. Therefore the discovery of drugs to treat glutamate excitotoxicity is an important goal. Here, we report that GNB is neuroprotective against glutamate-induced excitotoxicity...
October 8, 2016: European Journal of Pharmacology
Yingbo Fu, Yu Mu, Hui Lei, Pu Wang, Xin Li, Qiao Leng, Li Han, Xiaodan Qu, Zhanyou Wang, Xueshi Huang
Five novel tacrine-ferulic acid hybrid compounds (8a-e) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and chelating Cu(2+) were evaluated in vitro. Among them, 8c and 8d displayed the higher selectivity in inhibiting AChE over BuChE. Moreover, 8d also showed dramatic inhibition of self-Aβ aggregation, activity of chelating Cu(2+) and activity against Aβ-induced neurotoxicity in Neuro-2A cells...
October 11, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Megha Shah, Hetalkumar Shah, Atul Maslekar
We present here a case of 58-year-old male operated for coronary artery bypass graft surgery with four grafts. He developed neurologic symptoms with injection cefepime which recovered after withdrawal of the drug.
September 2016: Indian Journal of Pharmacology
Masahiko Funada
The number of law-evading chemical substances that pose serious health risks to humans is increasing worldwide, including Japan and the Western world, and their abuse is becoming a serious social problem. Analysis of the chemical substances in these herbal products revealed the presence of synthetic cannabinoids. This review summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids as a group of chemical substances contained in these products...
October 2016: Brain and Nerve, Shinkei Kenkyū No Shinpo
Emily Johnson, Yousef Hannawi, Nirma Carballido Martinez, Eva K Ritzl
Cefepime has been associated with encephalopathy and with nonconvulsive seizure activity, primarily in patients with renal impairment. Here, we report a case of cefepime-associated encephalopathy in a patient with normal renal function with stimulus-induced rhythmic activity seen on electroencephalogram, which resolved on discontinuation of cefepime. We bring this to the attention of the neurohospitalist community, as cefepime is widely used in the hospital setting, and cefepime-related neurotoxicity may go overlooked, especially in patients with normal renal function...
October 2016: Neurohospitalist
Akihiro Watanabe, Tsutomu Sasaki, Toshiro Yukami, Hideaki Kanki, Manabu Sakaguchi, Takemori Hiroshi, Kazuo Kitagawa, Hideki Mochizuki
There are no effective neuroprotectant drugs for acute cerebral ischemia. Serine racemase (SR) synthesizes d-serine, which is involved in N-methyl-d-aspartate (NMDA) receptor-induced neurotoxicity. Recently, SR deletion was reported to protect against focal cerebral ischemia. However, regulatory mechanisms controlling SR-activity in the neurovascular unit (NVU) during cerebral ischemia remain to be clarified. We investigated the effects of SR inhibition on neurovascular protection after ischemia. The SR inhibitor phenazine methosulfate (PMS) alleviated neuronal damage in an ex vivo ischemic model (oxygen glucose deprivation [OGD]) using primary neuronal cultures, and in an in vivo mouse model of ischemia (middle cerebral artery occlusion [MCAO])...
September 28, 2016: Neuroscience
Modesto de Candia, Giorgia Zaetta, Nunzio Denora, Domenico Tricarico, Maria Majellaro, Saverio Cellamare, Cosimo D Altomare
Several 6-substituted 3,4,5,6-tetrahydroazepino[4,3-b]indol-1(2H)-one (THAI) derivatives were synthesized and evaluated for their activity as cholinesterase (ChE) inhibitors. The most potent inhibitors were identified among 6-(2-phenylethyl)-THAI derivatives, and in particular compounds 12b and 12d proved to be very active against human BChE (IC50 = 13 and 1.8 nM, respectively), with 1000-fold selectivity over AChE. Structure-activity relationships highlighted critical features (e.g., ring fusion [4,3-b], integrity of the lactam CONH function) and favorable physicochemical properties of the 6-(2-phenylethyl) group (i...
September 13, 2016: European Journal of Medicinal Chemistry
W Huang, M Calvo, T Pheby, D L H Bennett, A S C Rice
HIV-associated sensory neuropathy (HIV-SN) is the most frequent manifestation of HIV disease. It often presents with significant neuropathic pain and is associated with previous exposure to neurotoxic nucleoside reverse transcriptase inhibitors. However, HIV-SN prevalence remains high even in resource-rich settings where these drugs are no longer used. Previous evidence suggests that exposure to indinavir, a protease inhibitor commonly used in antiretroviral therapy, may link to elevated HIV-SN risk. Here we investigated whether indinavir treatment was associated with the development of a "dying back" axonal neuropathy and changes in pain-relevant limb withdrawal and thigmotactic behaviours...
September 23, 2016: Pain
Vinod G Ugale, Sanjay B Bari
Anticonvulsants effective against multiple seizures are of wide interest as antiepileptic drugs, especially if active against pharmaco-resistant seizures. Herein, we synthesized 16 different, rationally designed 2-((6,7-dimethoxy-4-oxo-2-phenylquinazolin-3(4H)-yl)amino)-N-(substituted phenyl)acetamides and screened for anticonvulsant activities through in vivo experiments. Compound 4d emerged as prototype with excellent anti-seizure action in mice against electroshock, chemically induced and pharmaco-resistant 6-Hz seizure models with no symptoms of neurotoxicity and hepatotoxicity (ED50  = 23...
September 28, 2016: Archiv der Pharmazie
Li Yao, Shi-Xiao Peng, Yi-Da Xu, Stanley Li Lin, Yu-Hong Li, Chun-Jie Liu, Hou-De Zhao, Lin-Fang Wang, Yan-Qin Shen
1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), which induces the pathological characteristics of Parkinson's disease in rodents, also specifically targets dopaminergic neurons in zebrafish embryos and larvae. Loganin, a traditional Chinese drug, was reported to regulate immune function and possess anti-inflammatory and anti-shock effects. Here, we investigate the role of loganin in MPTP-induced Parkinson-like abnormalities in zebrafish. MPTP treatment-induced abnormal development, in larvae, such as pericardium edema, increased yolk color, yolk sac edema, and retarded yolk sac resorption, as well as defects in brain development...
September 23, 2016: Journal of Cellular Biochemistry
Victoria J Forster, Frederik W van Delft, Susan F Baird, Shona Mair, Roderick Skinner, Christina Halsey
PURPOSE: Methotrexate administration is associated with frequent adverse neurological events during treatment for childhood acute lymphoblastic leukemia. Here, we present evidence to support the role of common drug interactions and low vitamin B12 levels in potentiating methotrexate neurotoxicity. METHODS: We review the published evidence and highlight key potential drug interactions as well as present clinical evidence of severe methotrexate neurotoxicity in conjunction with nitrous oxide anesthesia and measurements of vitamin B12 levels among pediatric leukemia patients during therapy...
September 22, 2016: Cancer Chemotherapy and Pharmacology
Eugene A Kiyatkin, Hari Sharma
Methamphetamine (METH) is a powerful and often abused stimulant with potent addictive and neurotoxic properties. While it is generally believed that structural brain damage induced by METH results from oxidative stress, in this work we present data suggesting robust disruption of blood-brain and blood-spinal cord barriers (BBB and BSCB) during acute METH intoxication in rats. We demonstrate the relationships between METH-induced brain hyperthermia and widespread but structure-specific barrier leakage, acute glial activation, changes in brain water and ionic homeostasis, and structural damage of different types of cells in the brain and spinal cord...
September 20, 2016: CNS & Neurological Disorders Drug Targets
Elham Memari, Mohammad-Ali Hosseinian, Ali Mirkheshti, Ali Arhami-Dolatabadi, Mojtaba Mirabotalebi, Mohsen Khandaghy, Yahya Daneshbod, Leila Alizadeh, Sadegh Shirian
Injection of a variety of drugs such as local anesthetics (LAs) for peripheral nerve block has been shown to cause damage to peripheral nerves. Bupivacaine is a local anesthetic widely used in surgical procedures. The aim of this study was to evaluate the neurotoxicity of LAs including Bupivacaine and dexmedetomidine (DEX)-Bupivacaine on sciatic nerve tissue at histopathological level. In addition, we investigated whether perineural administration of DEX can attenuate Bupivacaine-induced neurotoxicity. Twenty adult Sprague Dawley rats received unilateral sciatic nerve blocks with either 0...
September 17, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Xu Wang, María Aránzazu Martínez, Qinghua Wu, Irma Ares, María Rosa Martínez-Larrañaga, Arturo Anadón, Zonghui Yuan
Fipronil (FIP) is widely used across the world as a broad-spectrum phenylpyrazole insecticide and veterinary drug. FIP was the insecticide to act by targeting the γ-aminobutyric acid (GABA) receptor and has favorable selective toxicity towards insects rather than mammals. However, because of accidental exposure, incorrect use of FIP or widespread FIP use leading to the contamination of water and soil, there is increasing evidence that FIP could cause a variety of toxic effects on animals and humans, such as neurotoxic, hepatotoxic, nephrotoxic, reproductive, and cytotoxic effects on vertebrate and invertebrates...
September 19, 2016: Critical Reviews in Toxicology
Marta Vicente-Rodríguez, Loreto Rojo Gonzalez, Esther Gramage, Rosalía Fernández-Calle, Ying Chen, Carmen Pérez-García, Marcel Ferrer-Alcón, María Uribarri, Alexis Bailey, Gonzalo Herradón
It was previously shown that mice with genetic deletion of the neurotrophic factor pleiotrophin (PTN-/-) show enhanced amphetamine neurotoxicity and impair extinction of amphetamine conditioned place preference (CPP), suggesting a modulatory role of PTN in amphetamine neurotoxicity and reward. We have now studied the effects of amphetamine (10mg/kg, 4 times, every 2h) in the striatum of mice with transgenic PTN overexpression (PTN-Tg) in the brain and in wild type (WT) mice. Amphetamine caused an enhanced loss of striatal dopaminergic terminals, together with a highly significant aggravation of amphetamine-induced increase in the number of GFAP-positive astrocytes, in the striatum of PTN-Tg mice compared to WT mice...
September 15, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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