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https://www.readbyqxmd.com/read/28537967/nortriptyline-enhances-morphine-conditioned-place-preference-in-neuropathic-rats-role-of-the-central-noradrenergic-system
#1
Wenli Mi, Shuxing Wang, Zerong You, Grewo Lim, Michael F McCabe, Hyangin Kim, Lucy Chen, Jianren Mao
BACKGROUND: Combination drug therapy is commonly used to treat chronic pain conditions such as neuropathic pain, and antidepressant is often used together with opioid analgesics. While rewarding is an intrinsic property of opioid analgesics, it is unknown whether the use of an antidepressant would influence opioid reward, which may contribute to opioid addiction. In this study, we examined whether nortriptyline (a tricyclic antidepressant and a first-line medication for neuropathic pain) would enhance the morphine rewarding property in both naive and chronic constriction sciatic nerve injury (CCI) rats...
May 19, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28535569/reinstituting-the-bolus-new-reasoning-for-an-existing-technique
#2
Porter W McRoberts, Jason E Pope, Catalina Apostol
Improved intrathecal (IT) pump technology is increasing the accuracy of IT opioid bolus dosing and promising advances in pain therapy. Opioid bolus dosing can be used with a minimal continuous infusion or it can function as the sole therapy. Bolus-only dosing is characterized by minimal use of opioid (often less than 1 mg of IT morphine). It achieves adequate pain control while reducing tolerance and possibly opioid-induced hyperalgesia. It may prevent receptor saturation, and provide a "washing out" of the opioid receptor that prevents the observed dose escalation resulting from continuous infusions...
May 2017: Pain Physician
https://www.readbyqxmd.com/read/28533693/dna-methylation-at-the-mu-1-opioid-receptor-gene-oprm1-promoter-predicts-preoperative-acute-and-chronic-postsurgical-pain-after-spine-fusion
#3
Vidya Chidambaran, Xue Zhang, Lisa J Martin, Lili Ding, Matthew T Weirauch, Kristie Geisler, Bobbie L Stubbeman, Senthilkumar Sadhasivam, Hong Ji
INTRODUCTION: The perioperative pain experience shows great interindividual variability and is difficult to predict. The mu-1 opioid receptor gene (OPRM1) is known to play an important role in opioid-pain pathways. Since deoxyribonucleic acid (DNA) methylation is a potent repressor of gene expression, DNA methylation was evaluated at the OPRM1 promoter, as a predictor of preoperative, acute, and chronic postsurgical pain (CPSP). METHODS: A prospective observational cohort study was conducted in 133 adolescents with idiopathic scoliosis undergoing spine fusion under standard protocols...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28533287/trv0109101-a-g-protein-biased-agonist-of-the-%C3%A2%C2%B5-opioid-receptor-does-not-promote-opioid-induced-mechanical-allodynia-following-chronic-administration
#4
Michael Koblish, Richard Carr, Edward R Siuda, David H Rominger, William Gowen-MacDonald, Conrad L Cowan, Aimee L Crombie, Jonathan D Violin, Michael W Lark
Prescription opioids are a mainstay in the treatment of acute moderate to severe pain. However, chronic use leads to a host of adverse consequences including tolerance and opioid-induced hyperalgesia (OIH), leading to more complex treatment regimens and diminished patient compliance. Patients experiencing OIH paradoxically experience exaggerated nociceptive responses instead of pain reduction after chronic opioid usage. The development of OIH and tolerance tend to occur simultaneously and, thus, present a challenge when studying the molecular mechanisms driving each phenomenon...
May 22, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28532680/decreased-spinal-endomorphin-2-contributes-to-mechanical-allodynia-in-streptozotocin-induced-diabetic-rats
#5
Le Niu, Guang-Hai Dai, Gao-Le He, Ming Yang, Hui-Min Hu, Zhong-Kai Liu, Nian-Song Qian, Yong-Liang Chen
Diabetic neuropathic pain (DNP) plays a major role in decreased life quality of diabetes patients, however, the neural mechanisms underlying DNP remain unclear. Endomorphins are the endogenous ligands for mu-opioid receptor. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, using a streptozotocin induced diabetic rat model that displayed obvious mechanical allodynia, it was found that the expression of spinal EM2 was significantly decreased in DNP rats...
May 19, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28531297/mechanisms-of-kappa-opioid-receptor-potentiation-of-dopamine-d2-receptor-function-in-quinpirole-induced-locomotor-sensitization-in-rats
#6
Angélica P Escobar, Marcela P González, Rodrigo C Meza, Verónica Noches, Pablo Henny, Katia Gysling, Rodrigo A España, José A Fuentealba, María E Andrés
Background: Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of Quinpirole (QNP), a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist (KOR). The mechanism underlying KOR potentiation of QNP-induced locomotor sensitization remains to be elucidated...
May 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28529734/differential-regulation-of-mouse-and-human-mu-opioid-receptor-gene-depends-on-the-single-stranded-dna-structure-of-its-promoter-and-%C3%AE-complex-protein-1
#7
Dong-Sun Lee, Ping-Yee Law, Wei Ln, Horace H Loh, Kyu Young Song, Hack Sun Choi
The Mu opioid receptor (MOR) mediates various functions of opioid-induced analgesia, euphoria and respiratory depression, and is a major target of opioid analgesics. Understanding of MOR gene expression among species is important for understanding its analgesic function in humans. In the current study, the polypyrimidine/polypurine (PPy/u) region, a key element of MOR gene expression, was compared in humans and mice. The mouse PPy/u element is highly homologous to its human element (84%), and the mouse MOR (mMOR) reporter drives luciferase activity 35-fold more effectively than the human MOR (hMOR) reporter...
May 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28529168/opioids-in-gastroenterology-treating-adverse-effects-and-creating-therapeutic-benefits
#8
Michael Camilleri, Anthony Lembo, David A Katzka
The use of opioid medications on both an acute and chronic basis is ubiquitous in the U.S. As opioid receptors densely populate the gastrointestinal tract, symptoms and side effects can be expected in these patients. In the esophagus, dysmotility may result manifesting with dysphagia and a syndrome indistinguishable from primary achalasia. In the stomach, a marked delay in gastric emptying may ensue with postprandial nausea and early satiety. Postoperatively, particularly with abdominal surgery, opioid induced ileus may ensue...
May 18, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28527855/initiation-of-extended-release-naltrexone-xr-ntx-for-opioid-use-disorder-prior-to-release-from-prison
#9
Peter D Friedmann, Donna Wilson, Randall Hoskinson, Michael Poshkus, Jennifer G Clarke
BACKGROUND: Opioid use disorder is common in prison populations, and prison release is a high-risk time for relapse and overdose. Initiation of extended release injectable naltrexone (XR-NTX)) prior to prison release might decrease relapse among opioid-dependent persons. OBJECTIVE: This pilot study examined the feasibility and acceptability of XR-NTX injection prior to prison release among adult inmates with opioid use disorder, followed by six months of community XR-NTX treatment...
April 19, 2017: Journal of Substance Abuse Treatment
https://www.readbyqxmd.com/read/28527421/a-phase-iii-randomized-multi-center-double-blind-placebo-controlled-study-of-safety-and-efficacy-of-lofexidine-for-relief-of-symptoms-in-individuals-undergoing-inpatient-opioid-withdrawal
#10
Charles W Gorodetzky, Sharon L Walsh, Peter R Martin, Andrew J Saxon, Kristen L Gullo, Kousick Biswas
BACKGROUND: Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. METHODS: Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal...
May 10, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28522254/novel-delta-opioid-receptor-agonists-with-oxazatricyclodecane-structure-showing-potent-agonistic-activities
#11
Kohei Hayashida, Shigeto Hirayama, Takashi Iwai, Yoshikazu Watanabe, Toshihiro Takahashi, Junichi Sakai, Eriko Nakata, Tomio Yamakawa, Hideaki Fujii, Hiroshi Nagase
We recently reported oxazatricyclodecane derivatives 1 as δ opioid receptor (DOR) agonists having a novel chemotype, but their DOR agonistic activities were relatively low. Based on the working hypothesis that the dioxamethylene moiety in 1 may be an accessory site and that it may interfere with the sufficient conformational change of the receptor required for exerting the full agonistic responses, we designed and synthesized new oxazatricyclodecane derivatives 2-4 lacking the dioxamethylene moiety. As we expected, the designed compounds 2-4 showed pronouncedly improved agonistic activities for the DOR...
April 19, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28514235/ondansetron-does-not-reduce-withdrawal-in-patients-with-physical-dependence-on-chronic-opioid-therapy
#12
Larry F Chu, John Sun, Anna Clemenson, Matthew J Erlendson, Tom Rico, Erika Cornell, Hannah Obasi, Zahra N Sayyid, Ellen M Encisco, Jeff Yu, Jamison G Gamble, Ian Carroll, J David Clark
OBJECTIVES: Individuals taking opioids for an extended period of time may become physically dependent, and will therefore experience opioid withdrawal should they stop taking the medication. Previous work in animal and human models has shown that the serotonin (5-HT3) receptor may be implicated in opioid withdrawal. In this study, we investigated if ondansetron, a 5-HT3-receptor antagonist, could reduce the symptoms of opioid withdrawal after chronic opioid exposure in humans. METHODS: In this double-blinded, randomized, crossover study, 33 chronic back pain patients (N = 33) were titrated onto sustained-release oral morphine for 30 days...
May 16, 2017: Journal of Addiction Medicine
https://www.readbyqxmd.com/read/28512665/involvement-of-%C3%A2%C2%B5-opioid-receptors-and-%C3%AE%C2%BA-opioid-receptors-in-itch-related-scratching-behaviour-of-imiquimod-induced-psoriasis-like-dermatitis-in-mice
#13
Nobuaki Takahashi, Mitsutoshi Tominaga, Ryohei Kosaka, Yayoi Kamata, Yoshie Umehara, Hironori Matsuda, Azumi Sakaguchi, Hideoki Ogawa, Kenji Takamori
The pathogenesis of psoriatic itch is poorly understood. The aim of this study was to investigate the involvement of opioid receptors in scratching behaviour of imiquimod-induced psoriasis-like dermatitis model mice. Topical application of 5% imiquimod cream to the rostral back skin of mice induced antihistamine-resistant scratching behaviour. The expression of µ-opioid receptor (MOR) protein increased in the epidermis, dorsal root ganglia (DRG) and spinal cord of imiquimod-treated mice. In contrast, the expression of κ-opioid receptor (KOR) protein decreased in the DRG and spinal cord of imiquimod-treated mice, and was undetectable in the epidermis of both groups...
May 17, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28511993/the-expression-of-opioid-genes-in-non-classical-reward-areas-depends-on-early-life-conditions-and-ethanol-intake
#14
Linnea Granholm, Aniruddah Todkar, Sofia Bergman, Kent Nilsson, Erika Comasco, Ingrid Nylander
The young brain is highly sensitive to environmental influences that can cause long-term changes in neuronal function, possibly through altered gene expression. The endogenous opioid system continues to mature after birth and because of its involvement in reward, an inadequate maturation of this system could lead to enhanced susceptibility for alcohol use disorder. Recent studies show that the classical reward areas nucleus accumbens and ventral tegmental area are less affected by early life stress whereas endogenous opioids in non-classical areas, e...
May 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28510066/the-delta-opioid-receptor-in-pain-control
#15
Khaled Abdallah, Louis Gendron
Nowadays, the delta opioid receptor (DOPr) represents a promising target for the treatment of chronic pain and emotional disorders. Despite the fact that they produce limited antinociceptive effects in healthy animals and in most acute pain models, DOPr agonists have shown efficacy in various chronic pain models. In this chapter, we review the progresses that have been made over the last decades in understanding the role played by DOPr in the control of pain. More specifically, the distribution of DOPr within the central nervous system and along pain pathways is presented...
May 17, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28509855/the-hypnotic-anxiolytic-and-antinociceptive-profile-of-a-novel-%C3%A2%C2%B5-opioid-agonist
#16
Guilherme Carneiro Montes, Bianca Nascimento Monteiro da Silva, Bismarck Rezende, Roberto Takashi Sudo, Vitor Francisco Ferreira, Fernando de Carvalho da Silva, Angelo da Cunha Pinto, Bárbara Vasconcellos da Silva, Gisele Zapata-Sudo
5'-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 1-12 were synthesized and a pharmacological screening of these derivatives was performed to identify a possible effect on the Central Nervous System (CNS) and to explore the associated mechanisms of action. The mice received a peritoneal injection (100 µmol/kg) of each of the 12 PILAB derivatives 10 min prior to the injection of pentobarbital and the mean hypnosis times were recorded. The mean hypnosis time increased for the mice treated with PILAB 8, which was prevented when mice were administered CTOP, a µ-opioid antagonist...
May 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28509375/chronic-nicotine-induced-changes-in-gene-expression-of-delta-and-kappa-opioid-receptors-and-their-endogenous-ligands-in-the-mesocorticolimbic-system-of-the-rat
#17
Muzeyyen Ugur, Egemen Kaya, Oguz Gozen, Ersin O Koylu, Lutfiye Kanit, Aysegul Keser, Burcu Balkan
Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are proposed as important mediators of nicotine reward. The present study investigated the regulatory effect of chronic nicotine treatment on the gene expression of DOR, KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were injected subcutaneously with nicotine at doses of 0.2, 0.4 or 0.6 mg/kg/day for six days. Rats were decapitated one hour after the last dose on day six, as this timing coincides with increased dopamine release in the mesocorticolimbic system...
May 16, 2017: Synapse
https://www.readbyqxmd.com/read/28508104/quercetin-inhibits-gout-arthritis-in-mice-induction-of-an-opioid-dependent-regulation-of-inflammasome
#18
Kenji W Ruiz-Miyazawa, Larissa Staurengo-Ferrari, Sandra S Mizokami, Talita P Domiciano, Fabiana T M C Vicentini, Doumit Camilios-Neto, Wander R Pavanelli, Phileno Pinge-Filho, Flávio A Amaral, Mauro M Teixeira, Rubia Casagrande, Waldiceu A Verri
We investigated the anti-inflammatory and analgesic effects of quercetin in monosodium urate crystals (MSU)-induced gout arthritis, and the sensitivity of quercetin effects to naloxone, an opioid receptor antagonist. Mice were treated with quercetin, and mechanical hyperalgesia was assessed at 1-24 h after MSU injection. In vivo, leukocyte recruitment, cytokine levels, oxidative stress, NFκB activation, and gp91(phox) and inflammasome components (NLRP3, ASC, Pro-caspase-1, and Pro-IL-1β) mRNA expression by qPCR were determined in the knee joints at 24 h after MSU injection...
May 15, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28506204/antibiotic-effects-of-loperamide-homology-of-human-targets-of-loperamide-with-targets-in-acanthamoeba-spp
#19
Abdul Mannan Baig, Zohaib Rana, M Mohsin Mannan, S Sumayya Tariq, H R Ahmad
BACKGROUND: Loperamide is an anti-diarrheal drug prescribed for non-infectious diarrhea. The drug is an opioid receptor agonist, a blocker of voltage-dependent calcium channel (Cav) and a calmodulin (CaM) inhibitor on human cells. Loperamide has been reported to exert anti-amoebic effects against pathogenic strains of Acanthamoeba castellanii. OBJECTIVES: The precise mode of antibiotic action, cellular target homology with human counterparts and the pattern of cell death induced by loperamide in Acanthamoeba castellanii remain to be established...
April 25, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/28504549/determination-of-naloxegol-in-human-biological-matrices
#20
Yan Li, Mark Hoffmann, Paul Severin
AIM: Naloxegol is an oral peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation. Sensitive, robust, bioanalytical methods were required to quantitate naloxegol in human biological matrices as part of the clinical development program. Results/methodology: Analytical plasma samples were prepared using Solid Phase Extraction (SPE) coupled with concentration. The method's linearity was established at 0.1-50 ng/ml with up to 100-fold dilution...
May 15, 2017: Bioanalysis
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