- Off-target effects of neuroleptics and antidepressants on Saccharomyces cerevisiae. [Journal Article]
- TSToxicol Sci 2017 Jan 13
- Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation,...
Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes. Moreover, the evolutionary conservation of many pathways allows the translation of yeast data to the human system. In this paper, a better attention was paid to chlorpromazine, as it still is one of the most widely used drug in therapy. The results of a toxicogenomic screening performed on a yeast mutants collection treated with chlorpromazine were instrumental to identify a set of genes for further analyses. For this purpose, a multidisciplinary approach was used based on growth phenotypes identification, Gene Ontology search, and network analysis. Then, the impacts of three antidepressants (imipramine, doxepin, and nortriptyline) and three neuroleptics (promazine, chlorpromazine, and promethazine) on S. cerevisiae were compared through physiological analyses, microscopy characterization, and transcriptomic studies. Data highlight key differences between neuroleptics and antidepressants, but also between the individual molecules. By performing a network analysis on the human homologous genes, it emerged that genes and proteins involved in the Notch pathway are possible off-targets of these molecules, along with key regulatory proteins.
- An update of management of insomnia in patients with chronic orofacial pain. [Review]
- ODOral Dis 2017 Jan 11
- In this review we discuss the management of chronic orofacial pain (COFP) patients with insomnia. Diagnostic work-up and follow-up routines of COFP patients should include assessment of sleep problem...
In this review we discuss the management of chronic orofacial pain (COFP) patients with insomnia. Diagnostic work-up and follow-up routines of COFP patients should include assessment of sleep problems. Management is based on a multidisciplinary approach, addressing the factors that modulate the pain experience as well as insomnia and including both non-pharmacological and pharmacological modalities. Parallel to treatment, patients should receive therapy for co-morbid medical and psychiatric disorders, and possible substance abuse that may be that may trigger or worsen the COFP and/or their insomnia. Insomnia treatment should begin with non-pharmacological therapy, to minimize potential side effects, drug interactions and risk of substance abuse associated with pharmacological therapy. Behavioral therapies for insomnia include: sleep hygiene, cognitive behavioral therapy for insomnia, multicomponent behavioral therapy or brief behavioral therapy for insomnia, relaxation strategies, stimulus control and sleep restriction. Approved U.S. Food and Drug Administration medications to treat insomnia include: benzodiazepines (estazolam, flurazepam, temazepam, triazolam and quazepam), non-benzodiazepine hypnotics (eszopiclone,zaleplon, zolpidem), the melatonin receptor agonist ramelteon, the antidepressant doxepin and the orexin receptor antagonist suvorexant. .Chronic orofacial pain can greatly improve following treatment of the underlying insomnia, and therefore, re-evaluation of COFP is advised after one month of treatment. This article is protected by copyright. All rights reserved.
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update. [Journal Article]
- CPClin Pharmacol Ther 2016 Dec 20
- CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and ...
CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for CYP2D6 and CYP2C19 genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants. This article is protected by copyright. All rights reserved.
- [A case of mediastinal emphysema following gastric lavage for oral doxepin poisoning]. [Journal Article]
- ZLZhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2016 Sep 20; 34(9):690-691
- Polythiophene/graphene oxide nanostructured electrodeposited coating for on-line electrochemically controlled in-tube solid-phase microextraction. [Journal Article]
- JCJ Chromatogr A 2016 Dec 02; 1475:8-17
- In this work, a novel polythiophene/graphene oxide (PTh/GO) nanostructured coating was introduced for on-line electrochemically-controlled in-tube solid phase microextraction of amitriptyline (AMI) a...
In this work, a novel polythiophene/graphene oxide (PTh/GO) nanostructured coating was introduced for on-line electrochemically-controlled in-tube solid phase microextraction of amitriptyline (AMI) and doxepin (DOX) as antidepressant drugs. The PTh/GO coating was prepared on the inner surface of a stainless steel tube by a facile in-situ electro-deposition method and it was used as a working electrode for electrochemically control in-tube solid phase microextraction. In the PTh/GO coating, GO acts as an anion dopant and sorbent. The PTh/GO coating, compared to PTh and GO coatings, exhibited enhanced long lifetime, good mechanical stability and a large specific surface area. Regarding the in-tube SPME, some important factors such as the extraction and desorption voltage, extraction and desorption times and flow rates of the sample solution and eluent, which could affect the extraction and separation efficiency of the analytes, were optimized. Total analysis time of this method including the online extraction and desorption time was about 21min for each sample. AMI and DOX were extracted, separated and determined with limits of detection as small as 0.3μgL(-1) and 0.5μgL(-1), respectively. This method showed good linearity in the range of 0.7-200μgL(-1), 2.3-200μgL(-1) and 2.9-200μgL(-1) for AMI, and in the range 0.9-200μgL(-1), 2.5-200μgL(-1) and 3.0-200μgL(-1) for DOX in water, urine and plasma samples, respectively; the coefficients of determination were also equal to or higher than 0.9976. The inter- and intra-assay precisions (RSD%, n=3) were in the range of 2.8-3.4% and 2.9-3.9% at the three concentration levels of 5, 25 and 50μgL(-1), respectively. Finally, under the optimal conditions, the method was applied for the analysis of the drugs in human urine and plasma pretreated samples and good results were obtained.
- Structural Analysis of the Histamine H1 Receptor. [Journal Article]
- HEHandb Exp Pharmacol 2016 Nov 09
- The crystal structure of the human histamine H1 receptor (H1R) has been determined in complex with its inverse agonist doxepin, a first-generation antihistamine. The crystal structure showed that dox...
The crystal structure of the human histamine H1 receptor (H1R) has been determined in complex with its inverse agonist doxepin, a first-generation antihistamine. The crystal structure showed that doxepin sits deeply inside the ligand-binding pocket and predominantly interacts with residues highly conserved among other aminergic receptors. This binding mode is considered to result in the low selectivity of the first-generation antihistamines for H1R. The crystal structure also revealed the mechanism of receptor inactivation by the inverse agonist doxepin. On the other hand, the crystal structure elucidated the anion-binding site near the extracellular portion of the receptor. This site consists of residues not conserved among other aminergic receptors, which are specific for H1R. Docking simulation and biochemical experimentation demonstrated that a carboxyl group on the second-generation antihistamines interacts with the anion-binding site. These results imply that the anion-binding site is a key site for the development of highly selective antihistamine drugs.
- Application of tandem dispersive liquid-liquid microextraction for the determination of doxepin, citalopram, and fluvoxamine in complicated samples. [Journal Article]
- JSJ Sep Sci 2016; 39(24):4828-4834
- A new type of dispersive liquid-liquid microextraction is used for the determination of doxepin, citalopram, and fluvoxamine in aqueous matrices. This method is based upon the tandem utilization of d...
A new type of dispersive liquid-liquid microextraction is used for the determination of doxepin, citalopram, and fluvoxamine in aqueous matrices. This method is based upon the tandem utilization of dispersive liquid-liquid microextraction, and by providing a high sample clean-up, it efficiently improves the applicability of the method in complicated matrices. For this purpose, in the first step, the analytes contained in an aqueous sample solution (8.0 mL) were extracted into an organic solvent, and then these analytes were simply back-extracted into an aqueous acceptor phase (50 μL). The overall extraction time was 7 min, and very simple tools were required for this aim. Optimization of the variables affecting the method such as the type and volume of the organic solvent used and effect of ionic strength was carried out to achieve the best extraction efficiency. Under the optimized experimental conditions, tandem dispersive liquid-liquid microextraction with high-performance liquid chromatography and UV detection showed a good linearity in the range of 10-5000 ng/mL. The limits of detection were in the range of 3-10 ng/mL. The Intra-day precisions (relative standard deviation) were 9.2, 4.5, and 4.8, and the recoveries were 58.5, 52.9, and 39.3% for citalopram, doxepin, and fluvoxamine, respectively.
- Modified biomolecule as potential vehicle for buccal delivery of doxepin. [Journal Article]
- TDTher Deliv 2016; 7(10):683-689
- CONCLUSIONS: Taking these findings into account, the modifications render this designed excipient fruitful for buccal delivery.
- Review of Safety and Efficacy of Sleep Medicines in Older Adults. [Review]
- CTClin Ther 2016; 38(11):2340-2372
- CONCLUSIONS: An ideal treatment for insomnia should help to improve sleep latency and sleep duration with limited awakenings and be without significant adverse effects such as daytime somnolence or decreased alertness. Cognitive behavioral therapy should always be first line treatment. Clinical inertia regarding previous prominent use of benzodiazepines and non-BzRAs will be a significant challenge for patients accustomed to their issuance. The future direction of insomnia treatment should have an emphasis on nonpharmacologic interventions, treating comorbid conditions, and focusing therapy on using benzodiazepines and non-BzRAs as last resorts.
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- Inappropriate prescribing in older persons: A systematic review of medications available in different criteria. [Review]
- AGArch Gerontol Geriatr 2017 Jan - Feb; 68:55-61
- CONCLUSIONS: The present study systematically compiled all medications included in 14 different criteria published last decade. Benzodiazepines, NSAIDs, antihistamines and antipsychotics were the most common drugs reported as potentially inappropriate for older persons. These results could help health professionals and panel experts to plan future criteria.