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https://www.readbyqxmd.com/read/28447863/lysophosphatidic-acid-and-amitriptyline-signal-through-lpa1r-to-reduce-p-glycoprotein-transport-at-the-blood-brain-barrier
#1
David B Banks, Gary Ny Chan, Rebecca A Evans, David S Miller, Ronald E Cannon
The blood-brain barrier is a microvascular network that (1) provides neuroprotection from metabolic and environmental toxins and (2) limits the delivery of therapeutics to the central nervous system (CNS). The ATP-binding cassette transporter P-glycoprotein contributes to the latter by actively pumping clinical substrates back into circulation before they can reach the brain parenchyma. Targeting P-glycoprotein has proven effective in increasing the delivery of therapeutics to their cerebral targets. We provide a novel mechanism to achieve this end in functioning, intact rat brain capillaries, whereby the bioactive phospholipid lysophosphatidic acid (LPA) and tricyclic antidepressant (TCA) amitriptyline reduce basal P-glycoprotein transport activity through a distinct lysophosphatidic acid 1 receptor-mediated signaling cascade that requires G-protein coupling, Src kinase, and ERK 1/2...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28438663/acute-effects-of-amitriptyline-on-adult-zebrafish-potential-relevance-to-antidepressant-drug-screening-and-modeling-human-toxidromes
#2
Konstantin A Demin, Tatiana O Kolesnikova, Sergey L Khatsko, Darya M Meshalkina, Evgeniya V Efimova, Yuri Yu Morzherin, Allan V Kalueff
The need to develop novel antidepressants is an emerging problem in biomedicine. An aquatic vertebrate species, the zebrafish (Danio rerio) may serve as a useful in-vivo screen for CNS drugs, and displays high sensitivity to a wide range of antidepressants. Amitriptyline is a commonly used tricyclic antidepressant which acts primarily as a serotonin and noradrenaline reuptake inhibitor. Here, we characterize drug-induced behavioral and neurochemical responses in adult zebrafish following their acute exposure to amitriptyline...
April 21, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28416380/spinal-dopaminergic-involvement-in-the-antihyperalgesic-effect-of-antidepressants-in-a-rat-model-of-neuropathic-pain
#3
Mi Chen, Hajime Hoshino, Shigeru Saito, Yang Yang, Hideaki Obata
Antidepressants such as tricyclic antidepressants, and serotonin noradrenaline reuptake inhibitors are a first-line treatment for neuropathic pain. Here, we aimed to determine the involvement of the spinal dopaminergic system in the antihyperalgesic effects of antidepressants in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). The right L5 spinal nerve of male Sprague-Dawley rats was ligated under inhalation anesthesia to induce hyperalgesia. Behavioral testing was performed by measuring ipsilateral hindpaw withdrawal thresholds after intraperitoneal injection of amitriptyline, duloxetine, milnacipran, and fluoxetine...
April 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28405886/pharmacokinetic-variability-of-drugs-used-for-prophylactic-treatment-of-migraine
#4
REVIEW
Peer Tfelt-Hansen, Frederik Nybye Ågesen, Agniezka Pavbro, Jacob Tfelt-Hansen
In this review, we evaluate the variability in the pharmacokinetics of 11 drugs with established prophylactic effects in migraine to facilitate 'personalized medicine' with these drugs. PubMed was searched for 'single-dose' and 'steady-state' pharmacokinetic studies of these 11 drugs. The maximum plasma concentration was reported in 248 single-dose and 115 steady-state pharmacokinetic studies, and the area under the plasma concentration-time curve was reported in 299 single-dose studies and 112 steady-state pharmacokinetic studies...
April 12, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28393897/olanzapine-but-not-clozapine-increases-glutamate-release-in-the-prefrontal-cortex-of-freely-moving-mice-by-inhibiting-d-aspartate-oxidase-activity
#5
Silvia Sacchi, Vito De Novellis, Giovanna Paolone, Tommaso Nuzzo, Monica Iannotta, Carmela Belardo, Marta Squillace, Paolo Bolognesi, Elena Rosini, Zoraide Motta, Martina Frassineti, Alessandro Bertolino, Loredano Pollegioni, Michele Morari, Sabatino Maione, Francesco Errico, Alessandro Usiello
D-aspartate levels in the brain are regulated by the catabolic enzyme D-aspartate oxidase (DDO). D-aspartate activates NMDA receptors, and influences brain connectivity and behaviors relevant to schizophrenia in animal models. In addition, recent evidence reported a significant reduction of D-aspartate levels in the post-mortem brain of schizophrenia-affected patients, associated to higher DDO activity. In the present work, microdialysis experiments in freely moving mice revealed that exogenously administered D-aspartate efficiently cross the blood brain barrier and stimulates L-glutamate efflux in the prefrontal cortex (PFC)...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28376226/urinary-concentrations-of-topically-administered-pain-medications
#6
Michele A Glinn, Andrew J Lickteig, Luke Weber, Sherri Recer, Matthew Salske, Audrey Harvey, Brian Rappold, Julie Stensland, Patrick Bell
A common treatment for chronic pain is prescription of analgesics, but their long-term use entails risk of morbidity, addiction and misuse. One way to reduce the risk of abuse is prescribing of analgesics in a topical form. Physicians are urged to perform urine drug testing to ensure that patients are compliant with their medication regimens. However, there is little data on the efficiency of transdermal delivery for many analgesic drugs, and no data on expected urine drug levels. This study includes data from over 29,000 specimens tested for gabapentin, ketamine, cyclobenzaprine or amitriptyline used orally or topically...
March 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28374970/human-bj-fibroblasts-is-an-alternative-to-mouse-balb-c-3t3-cells-in-in-vitro-neutral-red-uptake-assay
#7
Marika Mannerström, Tarja Toimela, Jertta-Riina Sarkanen, Tuula Heinonen
The OECD GD 129 BALB/c 3T3 Neutral Red Uptake (NRU) assay is a standardized test method for estimating starting dose for an acute oral systemic toxicity test in rodents. Mouse BALB/c 3T3 fibroblasts are the most commonly used cells in the NRU assay. We have previously transferred and validated BALB/c 3T3 NRU assay in our GLP laboratory. Subsequently, in order to obtain more human relevant cytotoxicity data, we performed an intra-laboratory validation using human BJ fibroblasts in the NRU assay instead of mouse BALB/c 3T3 fibroblasts...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28365034/capsaicin-8-patch-versus-oral-neuropathic-pain-medications-for-the-treatment-of-painful-diabetic-peripheral-neuropathy-a-systematic-literature-review-and-network-meta-analysis
#8
Floortje van Nooten, Maarten Treur, Krystallia Pantiri, Malcolm Stoker, Mata Charokopou
PURPOSE: A network meta-analysis (NMA) was performed, aiming to assess the relative efficacy and tolerability of the capsaicin 179-mg (8% weight for weight) cutaneous patch (capsaicin 8% patch) compared with oral, centrally acting agents (ie, pregabalin, gabapentin, duloxetine, amitriptyline) in patients with painful diabetic peripheral neuropathy (PDPN). METHODS: A systematic search of EMBASE/MEDLINE, Cochrane Library, and the National Health Service Centre for Reviews and Dissemination Database of Abstracts of Reviews of Effects was conducted to identify all randomized controlled trials...
March 29, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28358290/adsorption-of-selected-emerging-contaminants-onto-pac-and-gac-equilibrium-isotherms-kinetics-and-effect-of-the-water-matrix
#9
Francisco J Real, F Javier Benitez, Juan L Acero, Francisco Casas
The removal of three emerging contaminants (ECs) (amitriptyline hydrochloride (AH), methyl salicylate (MS) and 2-phenoxyethanol (PE)) dissolved in several water matrices by means of their adsorption onto powdered activated carbon (PAC) and granular activated carbon (GAC) has been investigated. When dissolved in ultrapure water, adsorption of the ECs followed the trend of AH > MS > PE, with a positive effect of the adsorbent dose. According to the analysis of the adsorption isotherms and adsorption kinetics, PAC showed strongly higher adsorption efficiency in both capacity and velocity of the adsorption, in agreement with its higher mesoporosity...
March 30, 2017: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/28350251/impact-of-cyp2d6-genotype-on-amitriptyline-efficacy-for-the-treatment-of-diabetic-peripheral-neuropathy-a-pilot-study
#10
Mamoonah Chaudhry, Marco Alessandrini, Jacobus Rademan, Tyren M Dodgen, Francois E Steffens, Danie G van Zyl, Andrea Gaedigk, Michael S Pepper
AIM: Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles. METHOD: To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced...
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28346213/development-and-application-of-a-high-performance-liquid-chromatography-stability-indicating-assay-for-beyond-use-date-determination-of-compounded-topical-gels-containing-multiple-active-drugs
#11
Gregory Gorman, Simara Sokom, Lori Coward, John J Arnold
Topical gels compounded by pharmacists are important clinical tools for the management of pain. Nevertheless, there is often a dearth of information about the chemical stability of drugs included in these topical formulations, complicating the assignment of beyond-use dating. The purpose of this study was to develop a high-performance liquid chromatography photodiode array-based stability-indicating assay that could simultaneously resolve six drugs (amitriptyline, baclofen, clonidine, gabapentin, ketoprofen, lidocaine) commonly included in topical gels for pain management and their potential degradation products...
March 2017: International Journal of Pharmaceutical Compounding
https://www.readbyqxmd.com/read/28343553/alpha-lipoic-acid-plus-omega-3-fatty-acids-for-vestibulodynia-associated-with-painful-bladder-syndrome
#12
Filippo Murina, Alessandra Graziottin, Raffaele Felice, Dania Gambini
OBJECTIVE: This study assessed the effectiveness of alpha lipoic acid (ALA) plus omega-3 polyunsaturated fatty acids (n-3 PUFAs) in combination with amitriptyline therapy in patients with vestibulodynia/painful bladder syndrome (VBD/PBS). METHODS: Women with VBD/PBS were randomly assigned to receive amitriptyline or amitriptyline plus a commercially available preparation (ALAnerv Age; Alfa Wassermann, Bologna, Italy) containing, in 2 capsules, ALA 600 mg plus docosahexaenoic acid 250 mg and eicosapentaenoic acid 16...
March 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
https://www.readbyqxmd.com/read/28342017/primary-localized-cutaneous-amyloidosis-a-systematic-treatment-review
#13
REVIEW
Till Weidner, Tanja Illing, Peter Elsner
BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement. Lichen amyloidosis, macular amyloidosis, and (primary localized cutaneous) nodular amyloidosis are different subtypes of PLCA. OBJECTIVE: The aim of this study was to review the current reported treatment options for PLCA. METHODS: This systematic review was based on a search in the PubMed database for English and German articles from 1985 to 2016...
March 24, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28340451/the-role-of-drug-drug-interactions-in-prostate-cancer-treatment-focus-on-abiraterone-acetate-prednisone-and-enzalutamide
#14
REVIEW
Marzia Del Re, Stefano Fogli, Lisa Derosa, Francesco Massari, Paul De Souza, Stefania Crucitta, Sergio Bracarda, Daniele Santini, Romano Danesi
Elderly patients with cancer may have comorbidities, each requiring additional pharmacologic treatment. Therefore, the occurrence of pharmacokinetic (PK) and pharmacodynamic (PD) interactions is very likely, and the risk of adverse reactions (ADRs), due to the narrow therapeutic window of anticancer drugs, is increased. Drug-drug interactions (DDIs) may occur in prostate cancer patients due to inhibition by abiraterone of liver cytochrome P450 (CYP)-dependent enzymes CYP2C8 and 2D6, which are involved in the metabolism of approximately 25% of all drugs, and induction by enzalutamide of CYP3A4, 2C9 and 2C19, which metabolize up to 50% of medications...
March 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28339378/stability-of-allopurinol-amitriptyline-hydrochloride-carbamazepine-domperidone-isoniazid-ketoconazole-lisinopril-naproxen-paracetamol-acetaminophen-and-sertraline-hydrochloride-in-syrspend-sf-ph4-oral-suspensions
#15
Hudson C Polonini, Sharlene Loures, Edson Peter de Araujo, Marcos Antônio F Brandão, Anderson O Ferreira
Oral liquids are safe alternatives to solid dosage forms, notably for elderly and pediatric patients that present dysphagia. The use of ready-to-use suspending vehicles such as SyrSpend SF PH4 is a suitable resource for pharmacists as they constitute a safe and timesaving option that has been studied often. The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients (allopurinol 20 mg/mL; amitriptyline hydrochloride 10 mg/mL; carbamazepine 25 mg/mL; domperidone 5 mg/mL; isoniazid 10 mg/mL; ketoconazole 20 mg/mL; lisinopril 1 mg/mL; naproxen 25 mg/mL; paracetamol [acetaminophen] 50 mg/mL; and sertraline hydrochloride 10 mg/mL) compounded in oral suspensions using SyrSpend SF PH4 as the vehicle throughout the study period and stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C)...
September 2016: International Journal of Pharmaceutical Compounding
https://www.readbyqxmd.com/read/28335658/dopamine-antagonists-for-treatment-resistance-in-autism-spectrum-disorders-review-and-focus-on-bdnf-stimulators-loxapine-and-amitriptyline
#16
REVIEW
Jessica A Hellings, L Eugene Arnold, Joan C Han
Drug development and repurposing are urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression and self-injury. Areas covered: We review dopamine antagonists, including classical and atypical, as well as unconventional antipsychotics in ASD. The older antipsychotic loxapine is discussed in terms of preliminary albeit limited evidence in ASD. Emerging promise of amitriptyline in ASD is discussed, together with promising BDNF effects of loxapine and amitriptyline...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28334783/amitriptyline-for-musculoskeletal-complaints-a-systematic-review
#17
Jacoline J van den Driest, Sita M A Bierma-Zeinstra, Patrick J E Bindels, Dieuwke Schiphof
Background.: The role of amitriptyline in musculoskeletal pain is not as clearly defined as in classical neuropathic pain conditions. Objective.: To assess the efficacy and effectiveness of amitriptyline in the treatment of pain in musculoskeletal complaints. Methods.: An extensive search (including Medline, Embase and Web of Science) was made up to April 2016 for randomised controlled trials on amitriptyline in musculoskeletal complaints compared to placebo, usual care, or other analgesic use...
April 1, 2017: Family Practice
https://www.readbyqxmd.com/read/28329903/-headache-treatment
#18
REVIEW
Hans Christoph Diener, Dagny Holle-Lee, Steffen Nägel, Charly Gaul
A precondition for the successful treatment of headaches is the correct headache diagnosis. Triptans are effective for attack treatment of migraine and cluster headache. However, there are not effective for the treatment of tension-type headache. For the prevention of frequent episodic migraine betablockers, flunarizine, topiramate and amitriptyline are recommended. For the prevention of chronic migraine evidence is only available for onabotulinumtoxinA and topiramate. For prophylactic treatment of tension-type headaches tricyclic antidepressants are used...
March 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28325395/topical-ketamine-amitriptyline-lidocaine-for-chronic-pruritus-a-retrospective-study-assessing-efficacy-and-tolerability
#19
Helen G Lee, Shoshana K Grossman, Rodrigo Valdes-Rodriguez, Francis Berenato, Jack Korbutov, Yiong-Huak Chan, Michael Joseph Lavery, Gil Yosipovitch
No abstract text is available yet for this article.
April 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28296334/a-study-on-cyp2c19-and-cyp2d6-polymorphic-effects-on-pharmacokinetics-and-pharmacodynamics-of-amitriptyline-in-healthy-koreans
#20
S Ryu, S Park, J H Lee, Y R Kim, H S Na, H S Lim, H Y Choi, I Y Hwang, J G Lee, Z W Park, W Y Oh, J M Kim, S E Choi
We performed a double-blinded, genotype-based stratification study to explore the pharmacokinetics and pharmacodynamics of amitriptyline according to CYP2C19 and CYP2D6 genotype in Korean subjects. Twenty-four healthy adults were grouped by genotype of CYP2C19 and CYP2D6. After a single dose of 25 mg of amitriptyline, blood samples were collected and anticholinergic effects were measured. The extent of N-demethylation of amitriptyline significantly decreased in subjects carrying two nonfunctional alleles of CYP2C19...
March 2017: Clinical and Translational Science
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