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TAK-994 Mechanistic Investigation into Drug-Induced Liver Injury.
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Takeda Development Center Americas, Inc, Cambridge, MA, USA.
The frequency of drug-induced liver injury (DILI) in clinical trials remains a challenge for drug developers despite advances in human hepatotoxicity models and improvements in reducing liver-related attrition in preclinical species. TAK-994, an oral orexin receptor 2 agonist, was withdrawn from phase II clinical trials due to the appearance of severe DILI. Here, we investigate the likely mechanism of TAK-994 DILI in hepatic cell culture systems examined cytotoxicity, mitochondrial toxicity, impact on drug transporter proteins, and covalent binding.
View Article and Find Full Text PDF[NMDA receptors in prelimbic cortex neurons projecting to paraventricular nucleus of the thalamus are associated with morphine withdrawal memory retrieval].
Sheng Li Xue Bao
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State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
At present, the problem of drug addiction treatment mainly lies in the high relapse rate of drug addicts. Addictive drugs will bring users a strong sense of euphoria and promote drug seeking. Once the drug is withdrawn, there will be withdrawal symptoms such as strong negative emotions and uncomfortable physical reactions.
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Biomedical Research Centre, University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic.
Tacrine is a centrally active non-competitive reversible acetylcholinesterase inhibitor. It also exerts antagonising activity against -methyl-D-aspartate receptors. Tacrine was approved for the treatment of Alzheimer's disease in 1993, but was withdrawn from clinical use in 2013 because of its hepatotoxicity and gastrointestinal side effects.
View Article and Find Full Text PDFPredicting the toxic side effects of drug interactions using chemical structures and protein sequences.
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View Article and Find Full Text PDFManagement and toxicological analysis of ocular hypertension after EyeCee ONE intraocular lens implantation: a case series.
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Department 3, 15-20 National Vision Hospital, IHU FOReSIGHT, 28 rue de Charenton, Paris, 75012, France.
Background: The EyeCee ONE intraocular lens (Nidek, Gamagori, Japan) has been withdrawn from the market due to a high number of reports of severe ocular hypertension (OHT) following phacoemulsification with implantation of this intraocular lens (IOL). In this case series, we report the results of a toxicological analysis and the surgical management of five patients with severe OHT following the implantation of defective EyeCee ONE IOLs during cataract surgery.
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