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https://www.readbyqxmd.com/read/29623611/m-trifluoromethyl-diphenyl-diselenide-regulates-prefrontal-cortical-mor-and-kor-protein-levels-and-abolishes-the-phenotype-induced-by-repeated-forced-swim-stress-in-mice
#1
Suzan Gonçalves Rosa, Ana Paula Pesarico, Franciele Martini, Cristina Wayne Nogueira
The present study aimed to investigate the m-trifluoromethyl-diphenyl diselenide [(m-CF3 -PhSe)2 ] effects on prefrontal cortical MOR and KOR protein levels and phenotype induced by repeated forced swim stress (FSS) in mice. Adult Swiss mice were subjected to repeated FSS sessions, and after that, they performed the spontaneous locomotor/exploratory activity, tail suspension, and splash tests. (m-CF3 -PhSe)2 (0.1 to 5 mg/kg) was administered to mice 30 min before the first FSS session and 30 min before the subsequent repeated FSS...
April 5, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29587571/-express-clinical-opioids-differentially-induce-co-internalization-of-%C3%AE-and-%C3%AE-opioid-receptors
#2
Fenghua Bao, Chang-Lin Li, Xu-Qiao Chen, Ying-Jin Lu, Lan Bao, Xu Zhang
Opioid receptors play an important role in mediating the spinal analgesia. The μ-opioid receptor (MOR) is the major target of opioid drugs widely used in clinics. However, the regulatory mechanisms of analgesic effect and tolerance for clinical MOR-targeting opioids remain to be fully investigated. Previous studies showed the interaction of δ-opioid receptor (DOR) with MOR to form the MOR/DOR heteromers that could be processed in the degradation pathway after DOR agonist treatment. Here we showed that clinical MOR-targeting opioids, morphine, fentanyl and methadone, but not tramadol, caused MOR co-internalization with DORs in both transfected human embryonic kidney 293 cells and primary sensory neurons...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29583107/morphine-reduces-mouse-microglial-engulfment-induced-by-lipopolysaccharide-and-interferon-%C3%AE-via-%C3%AE-opioid-receptor-and-p38-mitogen-activated-protein-kinase
#3
Jung-Hee Ryu, Sang-Hwan Do, Sung-Hee Han, Zhiyi Zuo
Objective To investigate the effects of morphine on microglial phagocytosis during neuroinflammation. Methods C8-B4 mouse microglial cells were exposed to various concentrations of morphine after the stimulation with lipopolysaccharide and interferon-γ and then fluorescent immunostaining was performed to assess the percentage of microglia that engulfed fluorescent microspheres in total microglia. Naloxone, β funaltrexamine, or naltrindole was used with 1 μM morphine to assess the involvement of specific opioid receptor...
March 27, 2018: Neurological Research
https://www.readbyqxmd.com/read/29575372/radar-plots-a-novel-modality-for-displaying-disparate-data-on-the-efficacy-of-eluxadoline-for-the-treatment-of-irritable-bowel-syndrome-with-diarrhea
#4
D M Brenner, L S Dove, D A Andrae, P S Covington, C Gutman, W D Chey
BACKGROUND: Patients with irritable bowel syndrome with diarrhea (IBS-D) experience a range of abdominal and bowel symptoms; successful management requires alleviation of this constellation of symptoms. Eluxadoline, a locally active mixed μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, is approved for the treatment of IBS-D in adults based on the results of 2 Phase 3 studies. Radar plots can facilitate comprehensive, visual evaluation of diverse but interrelated efficacy endpoints...
March 25, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29563057/opioid-receptor-and-%C3%AE-arrestin2-densities-and-distribution-change-after-sexual-experience-in-the-ventral-tegmental-area-of-male-rats
#5
René Garduño-Gutiérrez, Martha León-Olea, Gabriela Rodríguez-Manzo
Sexual experience modifies brain functioning and copulatory efficiency. Sexual activity, ejaculation in particular, is a rewarding behavior associated with the release of endogenous opioids, which modulate the activity of the mesolimbic dopaminergic system (MLS). In sexually exhausted rats, repeated ejaculation produces μ (MOR) and δ opioid receptor (DOR) internalization in ventral tegmental area (VTA) neurons, as well as long-lasting behavioral changes suggestive of brain plasticity processes. We hypothesized that in sexually naïve rats the endogenous opioids released during sexual experience acquisition, might contribute to brain plasticity processes involved in the generation of the behavioral changes induced by sexual experience...
May 15, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29560360/the-potentially-beneficial-central-nervous-system-activity-profile-of-ivacaftor-and-its-metabolites
#6
Elena K Schneider, Rachel M McQuade, Vincenzo C Carbone, Felisa Reyes-Ortega, John W Wilson, Brenda Button, Ayame Saito, Daniel P Poole, Daniel Hoyer, Jian Li, Tony Velkov
Ivacaftor-lumacaftor and ivacaftor are two new breakthrough cystic fibrosis transmembrane conductance modulators. The interactions of ivacaftor and its two metabolites hydroxymethylivacaftor (iva-M1) and ivacaftorcarboxylate (iva-M6) with neurotransmitter receptors were investigated in radioligand binding assays. Ivacaftor displayed significant affinity to the 5-hydroxytryptamine (5-HT; serotonin) 5-HT2C receptor (p K i =6.06±0.03), β3 -adrenergic receptor (p K i =5.71±0.07), δ-opioid receptor (p K i =5...
January 2018: ERJ Open Research
https://www.readbyqxmd.com/read/29501769/the-efficacy-of-a-lectin-from-abelmoschus-esculentus-depends-on-central-opioid-receptor-activation-to-reduce-temporomandibular-joint-hypernociception-in-rats
#7
Shirley Moreira Alves, Raul Sousa Freitas, Danielle Rocha do Val, Lorena Vasconcelos Vieira, Ellen Lima de Assis, Francisco Isaac Fernandes Gomes, Carlos Alberto de Almeida Gadelha, Tatiane Santi Gadelha, José Thalles Jocelino Gomes de Lacerda, Juliana Trindade Clemente-Napimoga, Vicente de Paulo Teixeira Pinto, Gerardo Cristino Filho, Mirna Marques Bezerra, Hellíada Vasconcelos Chaves
Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, e.g. inflammatory conditions. This study aimed to evaluate the efficacy of Abelmoschus esculentus lectin (AEL) in reducing formalin-induced temporomandibular joint inflammatory hypernociception in rats. The behavioral experiments were performed in male Wistar rats (180-240 g). Rats were pre-treated (i.v.) with AEL (0.001, 0.01 or 0.1 mg/kg) 30 min before formalin injection (i.art.). To analyze the possible effect of opioid pathways on AEL efficacy, animals were pre-treated with naloxone or CTOP (μ opioid receptor antagonist), naltrindole (δ opioid receptor antagonist) or nor-binaltorphimine (κ opioid receptor antagonist) (i...
March 1, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29496478/non-pharmacological-treatment-affects-neuropeptide-expression-in-neuropathic-pain-model
#8
Fabio Martinez Santos, Joyce Teixeira Silva, Igor Rafael Correia Rocha, Daniel Oliveira Martins, Marucia Chacur
Chronic constriction injury (CCI) of the sciatic nerve elicits changes in neuropeptide expression on the dorsal root ganglia (DRG). The neural mobilization (NM) technique is a noninvasive method that has been proven clinically effective in reducing pain. The aim of this study was to analyze the expression of substance P, transient receptor potential vanilloid 1 (TRPV1) and opioid receptors in the DRG of rats with chronic constriction injury and to compare it to animals that received NM treatment. CCI was performed on adult male rats...
May 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29441714/time-dependent-regional-brain-distribution-of-methadone-and-naltrexone-in-the-treatment-of-opioid-addiction
#9
Belin G Teklezgi, Annapurna Pamreddy, Sooraj Baijnath, Hendrik G Kruger, Tricia Naicker, Nirmala D Gopal, Thavendran Govender
Opioid addiction is a serious public health concern with severe health and social implications; therefore, extensive therapeutic efforts are required to keep users drug free. The two main pharmacological interventions, in the treatment of addiction, involve management with methadone an mu (μ)-opioid agonist and treatment with naltrexone, μ-opioid, kappa (κ)-opioid and delta (δ)-opioid antagonist. MET and NAL are believed to help individuals to derive maximum benefit from treatment and undergo a full recovery...
February 14, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29434817/%C3%AE-opioid-receptor-inhibition-prevents-remifentanil-induced-post-operative-hyperalgesia-via-regulating-glur1-trafficking-and-ampa-receptor-function
#10
Aifen Liu, Xiaopeng Wang, Hui Wang, Guoyi Lv, Yize Li, Hongmei Li
The interaction of remifentanil with glutamate systems has an important role in remifentanil-induced thermal and mechanical hyperalgesia. A previous study by our group suggested that the trafficking and function of glutamate receptor 1 (GluR1) subunits contributes to remifentanil-induced hyperalgesia by regulating the phosphorylation of GluR1 in dorsal horn neurons. The present study demonstrated that δ opioid receptor (DOR) inhibition prevented thermal and mechanical hyperalgesia, which was induced by remifentanil infusion via attenuating GluR1 subunit trafficking and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) function in dorsal horn neurons...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29432603/in-vitro-screening-for-seizure-liability-using-microelectrode-array-technology
#11
Jenifer A Bradley, Harry H Luithardt, Monica R Metea, Christopher J Strock
Drug induced seizure liabilities produce significant compound attrition during drug discovery. Currently available in vitro cytotoxicity assays cannot predict all toxicity mechanisms due to the failure of these assays to predict sublethal target specific electrophysiological liabilities. Identification of seizurogenic and other electrophysiological effects at early stages of the drug development process is important to ensure that safe candidate compounds can be developed while chemical design is taking place, long before these liabilities are discovered in costly preclinical in vivo studies...
February 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29374492/prediction-of-opioid-dose-in-cancer-pain-patients-using-genetic-profiling-not-yet-an-option-with-support-vector-machine-learning
#12
Anne Estrup Olesen, Debbie Grønlund, Mikkel Gram, Frank Skorpen, Asbjørn Mohr Drewes, Pål Klepstad
OBJECTIVE: Use of opioids for pain management has increased over the past decade; however, inadequate analgesic response is common. Genetic variability may be related to opioid efficacy, but due to the many possible combinations and variables, statistical computations may be difficult. This study investigated whether data processing with support vector machine learning could predict required opioid dose in cancer pain patients, using genetic profiling. Eighteen single nucleotide polymorphisms (SNPs) within the µ and δ opioid receptor genes and the catechol-O-methyltransferase gene were selected for analysis...
January 27, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29374140/microrna-874-suppresses-tumor-proliferation-and-metastasis-in-hepatocellular-carcinoma-by-targeting-the-dor-egfr-erk-pathway
#13
Yi Zhang, Yangchao Wei, Xuan Li, Xingsi Liang, Liming Wang, Jun Song, Xiuzhong Zhang, Chong Zhang, Jian Niu, Pengbo Zhang, Zeqiang Ren, Bo Tang
The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target of miR-874 via its 3' untranslated region (UTR). Moreover, miR-874 was downregulated in HCC and its expression was inversely correlated with DOR expression. Downregulation of miR-874 was also associated with larger tumor size, more vascular invasion, a poor TNM stage, poor tumor differentiation, and inferior patient outcomes...
January 26, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352503/in-vivo-effects-of-%C3%AE-opioid-receptor-agonist-%C3%AE-opioid-receptor-antagonist-peptidomimetics-following-acute-and-repeated-administration
#14
Jessica P Anand, Kelsey E Kochan, Anthony F Nastase, Deanna Montgomery, Nicholas W Griggs, John R Traynor, Henry I Mosberg, Emily M Jutkiewicz
BACKGROUND AND PURPOSE: Mu opioid receptor (μ-receptor) agonists are used for pain management, but produce adverse effects including tolerance, dependence, and euphoria. The co-administration of a μ-receptor agonist with a delta opioid receptor (δ-receptor) antagonist has been shown to produce antinociception with reduced development of some side effects. We characterized the effects of three μ-receptor agonist/δ-receptor antagonist peptidomimetics in vivo after acute and repeated administration to determine if this profile provides a viable alternative to traditional opioid analgesics...
January 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29342943/the-peptide-pnpp-19-a-spider-toxin-derivative-activates-%C3%AE-opioid-receptors-and-modulates-calcium-channels
#15
Ana C N Freitas, Steve Peigneur, Flávio H P Macedo, José E Menezes-Filho, Paul Millns, Liciane F Medeiros, Maria A Arruda, Jader Cruz, Nicholas D Holliday, Jan Tytgat, Gareth Hathway, Maria E de Lima
The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin δ-CNTX-Pn1c (PnTx2-6), isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests suggest that PnPP-19 induces antinociception by activation of CB1, μ and δ opioid receptors. Since the peripheral and central antinociception induced by PnPP-19 involves opioid activation, the aim of this work was to identify whether this synthetic peptide could directly activate opioid receptors and investigate the subtype selectivity for μ-, δ- and/or κ-opioid receptors...
January 15, 2018: Toxins
https://www.readbyqxmd.com/read/29340866/-in-silico-study-of-the-binding-of-two-novel-antagonists-to-the-nociceptin-receptor
#16
Stefano Della Longa, Alessandro Arcovito
Antagonists of the nociceptin receptor (NOP) are raising interest for their possible clinical use as antidepressant drugs. Recently, the structure of NOP in complex with some piperidine-based antagonists has been revealed by X-ray crystallography. In this study, a multi-flexible docking (MF-docking) procedure, i.e. docking to multiple receptor conformations extracted by preliminary molecular dynamics trajectories, together with hybrid quantum mechanics/molecular mechanics (QM/MM) simulations have been carried out to provide the binding mode of two novel NOP antagonists, one of them selective (BTRX-246040, formerly named LY-2940094) and one non selective (AT-076), i...
January 16, 2018: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29302220/a-brief-review-of-the-genetics-and-pharmacogenetics-of-opioid-use-disorders
#17
Wade Berrettini
Increased physician prescribing of opioids to treat chronic nonprogressive pain has been accompanied by an increase in opioid addiction. Twin studies of opioid addiction are consistent with an inherited component of risk, approximately 50%. Several genome-wide association study (GWAS) reports indicate that genetic risk for opioid addiction is conveyed by many alleles of small effect (odds ratios <1.5). These reports have detected alleles in potassium-ion-channel genes ( KCNC1 and KCNG2 ) and in a glutamate receptor auxiliary protein (CNIH3)...
September 2017: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/29288267/pi3k-akt-pathway-a-role-in-%C3%AE-opioid-receptor-mediated-rgc-neuroprotection
#18
Shahid Husain, Anis Ahmad, Sudha Singh, Carolyn Peterseim, Yasir Abdul, Matthew J Nutaitis
Purpose: This study examines the role of PI3K/Akt pathway in δ-opioid receptor agonist (SNC-121)-induced RGC neuroprotection in a chronic glaucoma rat model. Methods: Injecting hypertonic saline into the limbal veins of Brown Norway rats elevated IOP. Rats were treated either with 1 mg/kg SNC-121 or 3 mg/kg 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY-294002; PI3K/Akt inhibitor) plus SNC-121 once daily for 7 days. Pattern ERGs were recorded in response to contrast reversal of patterned visual stimuli...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29262398/characteristic-microrna-expression-induced-by-%C3%AE-opioid-receptor-activation-in-the-rat-liver-under-prolonged-hypoxia
#19
Feng Zhi, Naiyuan Shao, Lian Xue, Yuan Xu, Xuezhi Kang, Yilin Yang, Ying Xia
BACKGROUND/AIMS: Hypoxic/ischemic injury to the liver is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ ischemic events, and δ-opioid receptor (DOR) is protective against hypoxic/ischemic injury, we asked if pharmacological activation of DOR can alter hypoxic events by regulating miRNA expression in the liver. As the first step, the present work aimed at testing the effect of DOR activation on hepatic miRNA expression in hypoxia...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29193080/the-non-peptidic-%C3%AE-opioid-receptor-agonist-tan-67-mediates-neuroprotection-post-ischemically-and-is-associated-with-altered-amyloid-precursor-protein-expression-maturation-and-processing-in-mice
#20
Jia-Wei Min, Yanying Liu, David Wang, Fangfang Qiao, Hongmin Wang
Tan-67 is a selective non-peptidic δ-opioid receptor (DOR) agonist that confers neuroprotection against cerebral ischemia/reperfusion (I/R)-caused neuronal injury in pre-treated animals. In this study, we examined whether post-ischemic administration of Tan-67 in stroke mice is also neuroprotective and whether the treatment affects expression, maturation and processing of the amyloid precursor protein (APP). A focal cerebral I/R model in mice was induced by middle cerebral artery occlusion for 1 h and Tan-67 (1...
February 2018: Journal of Neurochemistry
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