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https://www.readbyqxmd.com/read/29149731/purinergic-drug-targets-for-gastrointestinal-disorders
#1
REVIEW
Geoffrey Burnstock, Kenneth A Jacobson, Fievos L Christofi
Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. Gut inflammation releases ATP that acts on neuronal, glial, epithelial and immune cells. Purinergic signalling in glia and neurons is implicated in enteric neuropathies. Inflammation activates glia to increase ATP release and alter purinergic signalling. ATP release causes neuron death and gut motor dysfunction in colitis via a P2X7-dependent neural-glial pathway and a glial purinergic-connexin-43 pathway...
November 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29149605/bias-factor-and-therapeutic-window-correlate-to-predict-safer-opioid-analgesics
#2
Cullen L Schmid, Nicole M Kennedy, Nicolette C Ross, Kimberly M Lovell, Zhizhou Yue, Jenny Morgenweck, Michael D Cameron, Thomas D Bannister, Laura M Bohn
Biased agonism has been proposed as a means to separate desirable and adverse drug responses downstream of G protein-coupled receptor (GPCR) targets. Herein, we describe structural features of a series of mu-opioid-receptor (MOR)-selective agonists that preferentially activate receptors to couple to G proteins or to recruit βarrestin proteins. By comparing relative bias for MOR-mediated signaling in each pathway, we demonstrate a strong correlation between the respiratory suppression/antinociception therapeutic window in a series of compounds spanning a wide range of signaling bias...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29147138/an-update-on-prucalopride-in-the-treatment-of-chronic-constipation
#3
REVIEW
Anam Omer, Eamonn M M Quigley
Chronic constipation (CC) is a highly prevalent and often under-appreciated gastrointestinal disorder associated with significant impairment in quality of life. Symptoms of constipation are typically present for a number of years prior to a patient seeking help. Lifestyle modifications followed by, or coupled with, over-the-counter laxatives represent the initial treatment option; however, relief for many is limited and dissatisfaction rates for these approaches remain high. Over recent years, therefore, considerable effort has been exerted on the development of novel pharmacological approaches...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29146238/ccr5-mediates-hiv-1-tat-induced-neuroinflammation-and-influences-morphine-tolerance-dependence-and-reward
#4
Maciej Gonek, Virginia D McLane, David L Stevens, Kumiko Lippold, Hamid I Akbarali, Pamela E Knapp, William L Dewey, Kurt F Hauser, Jason J Paris
The HIV-1 regulatory protein, trans-activator of transcription (Tat), interacts with opioids to potentiate neuroinflammation and neurodegeneration within the CNS. These effects may involve the C-C chemokine receptor type 5 (CCR5); however, the behavioral contribution of CCR5 on Tat/opioid interactions is not known. Using a transgenic murine model that expresses HIV-1 Tat protein in a GFAP-regulated, doxycycline-inducible manner, we assessed morphine tolerance, dependence, and reward. To assess the influence of CCR5 on these effects, mice were pretreated with oral vehicle or the CCR5 antagonist, maraviroc, prior to morphine administration...
November 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29146030/pain-in-birds-the-anatomical-and-physiological-basis
#5
REVIEW
Jamie M Douglas, David Sanchez-Migallon Guzman, Joanne R Paul-Murphy
This article reviews the current understanding of the anatomy and physiology of pain in birds, with consideration of some of its differences from mammalian pain. From transduction to transmission, modulation, projection, and perception, birds possess the neurologic components necessary to respond to painful stimuli and they likely perceive pain in a manner similar to mammals. This article also describes the current understating of opioid receptors, inflammatory mediators, and additional factors in the modulation of pain in avian species...
January 2018: Veterinary Clinics of North America. Exotic Animal Practice
https://www.readbyqxmd.com/read/29146025/pain-and-its-control-in-reptiles
#6
REVIEW
Sean M Perry, Javier G Nevarez
Reptiles have the anatomic and physiologic structures needed to detect and perceive pain. Reptiles are capable of demonstrating painful behaviors. Most of the available literature indicates pure μ-opioid receptor agonists are best to provide analgesia in reptiles. Multimodal analgesia should be practiced with every reptile patient when pain is anticipated. Further research is needed using different pain models to evaluate analgesic efficacy across reptile orders.
January 2018: Veterinary Clinics of North America. Exotic Animal Practice
https://www.readbyqxmd.com/read/29144441/g-protein-coupled-receptors-targeted-by-analgesic-venom-peptides
#7
REVIEW
James T Daniel, Richard J Clark
Chronic pain is a complex and debilitating condition associated with a large personal and socioeconomic burden. Current pharmacological approaches to treating chronic pain such as opioids, antidepressants and anticonvulsants exhibit limited efficacy in many patients and are associated with dose-limiting side effects that hinder their clinical use. Therefore, improved strategies for the pharmacological treatment of pathological pain are urgently needed. G-protein coupled receptors (GPCRs) are ubiquitously expressed on the surface of cells and act to transduce extracellular signals and regulate physiological processes...
November 16, 2017: Toxins
https://www.readbyqxmd.com/read/29143891/in-search-of-the-ideal-promotility-agent-optimal-use-of-currently-available-promotility-agents-for-nutrition-therapy-of-the-critically-ill-patient
#8
REVIEW
Sarah J Diamond, Endashaw Omer, Laszlo Kiraly
PURPOSE OF REVIEW: Enteral nutrition therapy is essential in the management of critically ill patients. Prokinetic agents have been used successfully to aid in the delivery of nutrition and improve feeding tolerance in patients in the intensive care unit (ICU). The aim of this report is to review the existing promotility agents available for use in the critically ill as well as outline the role of potential investigative drugs in order to provide a guide to the management of this difficult and important clinical dilemma...
November 16, 2017: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/29143802/the-inhibitory-effects-of-cobalt-protoporphyrin-ix-and-cannabinoid-2-receptor-agonists-in-type-2-diabetic-mice
#9
Christina McDonnell, Sergi Leánez, Olga Pol
The activation of the transcription factor Nrf2 inhibits neuropathy and modulates the activity of delta-opioid receptors (DOR) in type 2 diabetic mice but the impact of Nrf2/HO-1 pathway on the antinociceptive actions of cannabinoid 2 receptors (CB2R) has not been assessed. Using male mice BKS.Cg-m+/+Leprdb/J (db/db) we investigated if treatment with cobalt protoporphyrin IX (CoPP), an HO-1 inductor, inhibited mechanical allodynia, hyperglycemia and obesity associated to type 2 diabetes. The antinociceptive effects of JWH-015 and JWH-133 (CB2R agonists) administered with and without CoPP or sulforaphane (SFN), a Nrf2 transcription factor activator, have been also evaluated...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29142121/the-role-of-kappa-opioid-receptors-in-glutamate-input-selection-in-the-ventral-striatum
#10
Angelica P Escobar
No abstract text is available yet for this article.
November 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29141871/potential-approaches-to-prevent-hypoglycemia-associated-autonomic-failure
#11
REVIEW
Eric Lontchi-Yimagou, Jee Young You, Michelle Carey, Ilan Gabriely, Harry Shamoon, Meredith Hawkins
Clear health benefits are associated with intensive glucose control in type 1 diabetes mellitus (T1DM). However, maintaining near-normal glycemia remains an elusive goal for many patients, in large part owing to the risk of severe hypoglycemia. In fact, recurrent episodes of hypoglycemia lead to 'hypoglycemia-associated autonomic failure' (HAAF), characterized by defective counter-regulatory responses to hypoglycemia. Extensive studies to understand the mechanisms underlying HAAF have revealed multiple potential etiologies, suggesting various approaches to prevent the development of HAAF...
November 14, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29141251/opioid-receptors-contribute-to-antinociceptive-effect-of-tianeptine-on-colorectal-distension-induced-visceral-pain-in-rats
#12
S Sırrı Bilge, Fatih İlkaya, Özge Darakcı, Engin Çiftcioğlu, Ayhan Bozkurt
Tianeptine is a clinically effective atypical antidepressant with distinct neurochemical properties. In this study, we aimed to investigate the contribution of opioid receptors in the antinociceptive effect of tianeptine on visceral pain in awake rats and to differentiate the subtype and the localization (central and/or peripheral) of these opioid receptors involved in this antinociception. Visceromotor response to noxious colorectal distension (CRD) was quantified with electromyographic recordings, obtained from previously implanted electrodes into the external oblique musculature of rats under anesthesia, before and after tianeptine administration...
November 15, 2017: Pharmacology
https://www.readbyqxmd.com/read/29138268/n-acyl-amino-acids-elmiric-acids-endogenous-signaling-molecules-with-therapeutic-potential
#13
Sumner Burstein
The subject of N-acyl amino acid conjugates has been rapidly growing in recent years, especially with regard to their analgesic and anti-inflammatory actions. The field is comprised of a large family of lipid signaling molecules whose importance is only now being fully realized. The most widely studied member is N-arachidonoyl glycine (NAGly), which differs structurally from the endocannabinoid anandamide (N-arachidonoyl ethanolamide) by a single oxygen atom and the two are metabolically related. Topics that are covered in this mini review are: biosynthetic pathways for N-acyl amino acids, receptors for N-acyl amino acids, physiological actions of N-acyl amino acids, pharmacological effects of N-acyl amino acids and molecular mechanisms believed to be responsible for their effects...
November 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29137427/association-of-opioid-receptor-mu-1-oprm1-a118g-polymorphism-rs1799971-with-nicotine-dependence
#14
Xiangyi Kong, Hao Deng, Theodore Alston, Yanguo Kong, Jingping Wang
Background and Object: Whether opioid-receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) is associated with nicotine dependence is controversial. We analyzed the combined results from published studies of this possibility. Methods: Literature reviews were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Web of Science, Chinese National Science Infrastructure (CNKI), PubMed, Embase and Google Scholar database searches using MeSH terms were conducted to find all relevant researches up to October 2016...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137290/expression-of-protein-kinase-a-and-the-kappa-opioid-receptor-in-selected-brain-regions-and-conditioned-place-aversion-in-morphine-dependent-rats
#15
Xiuhua Song, Wenqiang Li, Yuzhong Shi, Jingdan Zhang, Yi Li
This study examined adaptive changes in protein kinase A (PKA) and kappa opioid receptor (KOR) in selected addiction-related brain regions before and after conditioned place aversion (CPA). Seventy-two male SD rats were randomly assigned to an experimental group (morphine + naloxone, "MN") and 2 control groups: MS (morphine + saline) and SN (saline + naloxone). MN rats were intraperitoneally injected with morphine twice per day for 6.5 days and naloxone once and trained to establish CPA model. MS and SN rats were injected with equivalent volumes of morphine plus saline and saline plus naloxone, respectively...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136763/amorphous-solid-dispersions-of-hecogenin-acetate-using-different-polymers-for-enhancement-of-solubility-and-improvement-of-anti-hyperalgesic-effect-in-neuropathic-pain-model-in-mice
#16
Carlos Demócedes Luís de França Almeida Moreira, Jonas Gabriel de Oliveira Pinheiro, Walter Ferreira da Silva-Júnior, Euzébio Guimarães Barbosa, Zênia Maria Maciel Lavra, Erick Willyame Menezes Pereira, Marília Matos Resende, Eduardo Pereira de Azevedo, Lucindo José Quintans-Júnior, Adriano Antunes de Souza Araújo, Jullyana de Souza Siqueira Quintans, Ádley Antonini Neves de Lima
Hecogenin acetate (HA) is an acetylated sapogenin that has shown potential antihyperalgesic activity, inhibiting descending pain and acting in opioid receptors. However, HA exhibits poor aqueous solubility, which may limit its application. This study aims to develop amorphous solid dispersions (ASD) using five hydrophilic polymers, to characterize them and to evaluate their antihyperalgesic activity. Physicochemical characterization was performed by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Fourier Transformed Infrared (FTIR) spectroscopy...
November 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29135018/chronic-prurigo-of-nodular-type-a-review
#17
Claudia Zeidler, Athanasios Tsianakas, Manuel Pereira, Hartmut Ständer, Gil Yosipovitch, Sonja Ständer
Prurigo nodularis (PN) is a subtype of chronic prurigo presenting single to multiple symmetrically distributed, hyperkeratotic and intensively itching papules and nodules. PN evolves along with chronic pruritus in the context of diverse dermatological, systemic, neurological or psychiatric conditions. Permanent scratching is possibly a major trigger of PN, although its exact pathophysiology remains unclear. Current state-of-the-art therapy for PN consists of topical steroids, capsaicin, calcineurin inhibitors, ultraviolet (UV) therapy, systemic administration of gabapentinoids, μ-opioid receptor antagonists, antidepressants or immunosuppressants...
August 23, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29133887/a-complementary-scale-of-biased-agonism-for-agonists-with-differing-maximal-responses
#18
Javier Burgueño, Marta Pujol, Xavier Monroy, David Roche, Maria Jose Varela, Manuel Merlos, Jesús Giraldo
Compelling data in the literature from the recent years leave no doubt about the pluridimensional nature of G protein-coupled receptor function and the fact that some ligands can couple with different efficacies to the multiple pathways that a receptor can signal through, a phenomenon most commonly known as functional selectivity or biased agonism. Nowadays, transduction coefficients (log(τ/KA)), based on the Black and Leff operational model of agonism, are widely used to calculate bias. Nevertheless, combining both affinity and efficacy in a single parameter can result in compounds showing a defined calculated bias of one pathway over other though displaying varying experimental bias preferences...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29132133/endomorphins-promising-endogenous-opioid-peptides-for-the-development-of-novel-analgesics
#19
Zheng-Hui Gu, Bo Wang, Zhen-Zhen Kou, Yang Bai, Tao Chen, Yu-Lin Dong, Hui Li, Yun-Qing Li
Endomorphin-1 (EM1) and endomorphin-2 (EM2) are two endogenous ligands that belong to the opioid peptide family and have the highest affinity and selectivity for the µ-opioid receptor (MOR). The neuroanatomical distribution, ultrastructural features and neural circuitry of EM-containing neuronal structures have been morphologically demonstrated. In addition, the modulation effects of the EMs in different areas reflect their potential endogenous roles in many major physiological processes, including their remarkable roles in the transmission and modulation of noxious information...
November 13, 2017: Neuro-Signals
https://www.readbyqxmd.com/read/29131554/the-pathophysiology-incidence-impact-and-treatment-of-opioid-induced-nausea-and-vomiting
#20
Theresa Mallick-Searle, Mechele Fillman
PURPOSE: Opioid medications are integral in managing acute moderate-to-severe pain. Opioid analgesics bind to μ (mu), κ (kappa), or δ (delta) opioid receptors in the brain, spinal cord, and digestive tract. However, opioids cause adverse effects that may interfere with their therapeutic use. Some adverse effects wane over time, but patients using opioids for acute pain struggle with opioid-induced nausea and vomiting (OINV) the entire time they take the opioid. This article discusses the underlying mechanisms, clinical implications, and treatment strategies of OINV...
November 2017: Journal of the American Association of Nurse Practitioners
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