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https://www.readbyqxmd.com/read/28734904/identifying-novel-members-of-the-wntless-interactome-through-genetic-and-candidate-gene-approaches
#1
Jessica Petko, Trevor Tranchina, Goral Patel, Robert Levenson, Stephanie Justice-Bitner
Wnt signaling is an important pathway that regulates several aspects of embryogenesis, stem cell maintenance, and neural connectivity. We have recently determined that opioids decrease Wnt secretion, presumably by inhibiting the recycling of the Wnt trafficking protein Wntless (Wls). This effect appears to be mediated by protein-protein interaction between Wls and the mu-opioid receptor (MOR), the primary cellular target of opioid drugs. The goal of this study was to identify novel protein interactors of Wls that are expressed in the brain and may also play a role in reward or addiction...
July 19, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28734766/trpv1-modulates-morphine-induced-conditioned-place-preference-via-p38-mapk-in-the-nucleus-accumbens
#2
Sa-Ik Hong, Thi-Lien Nguyen, Shi-Xun Ma, Hyoung-Chun Kim, Seok-Yong Lee, Choon-Gon Jang
Emerging evidence suggests that the transient receptor potential vanilloid type 1 channel (TRPV1) is a novel target for the treatment of drug addiction, such as cocaine and morphine. Previously we reported that TRPV1 inhibition reduced morphine reward in the dorsal striatum (DSt) of mice and morphine self-administration through a decrease in accumbal activity in rats. However, the role of TRPV1 on morphine-conditioned reward in addiction-related brain regions, such as the nucleus accumbens (NAc), has not been previously established...
July 19, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28734765/ampakines-and-morphine-provide-complementary-analgesia
#3
Yongjun Sun, Kevin Liu, Erik Martinez, Jahrane Dale, Dong Huang, Jing Wang
Glutamate signaling in the central nervous system is known to play a key role in pain regulation. AMPAkines can enhance glutamate signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. previous studies have shown that AMPAkines are effective analgesic agents, and their site of action is likely in the brain. It is not known, however, if AMPAkines can provide complementary analgesia in combination with opioids, the most commonly used analgesics. Here, we show that the co-administration of an AMPAkine with morphine can provide additional analgesia, both in naïve rats and in rats that experience postoperative pain...
July 19, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28734666/development-of-novel-lp1-based-analogues-with-enhanced-delta-opioid-receptor-profile
#4
Lorella Pasquinucci, Rita Turnaturi, Orazio Prezzavento, Emanuela Arena, Giuseppina Aricò, Zafiroula Georgoussi, Rosalba Parenti, Giuseppina Cantarella, Carmela Parenti
Pain relief achieved by co-administration of drugs acting at different targets is more effective than that obtained with conventional MOR selective agonists usually associated to relevant side effects. It has been demonstrated that simultaneously targeting different opioid receptors is a more effective therapeutic strategy. Giving the promising role for DOR in pain management, novel LP1-based analogues with different N-substituents were designed and synthesized with the aim to improve DOR profile. For this purpose, we maintained the phenyl ring in the N-substituent of 6,7-benzomorphan scaffold linked to an ethyl spacer bearing a hydroxyl/methyl or methoxyl group at carbon 2 or including it in a 1,4-benzodioxane ring...
July 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28732166/mel-n16-a-series-of-novel-endomorphin-analogs-with-good-analgesic-activity-and-a-favorable-side-effect-profile
#5
Xin Liu, Long Zhao, Yuan Wang, Jingjing Zhou, Dan Wang, Yixin Zhang, Xianghui Zhang, Zhaojuan Wang, Dongxu Yang, Lingyun Mou, Rui Wang
Opioid peptides are neuromodulators that bind to opioid receptors and reduce pain sensitivity. Endomorphins are one of the most active endogenous opioid peptides, and they have good affinity and selectivity toward the μ opioid receptor. However, their clinical usage is hindered by their inability to cross the blood-brain barrier, and their poor in vivo activity after peripheral injection. In order to overcome these defects, we have designed and synthesized a series of novel endomorphin analogs with multiple site modifications...
July 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28731926/history-of-anaesthesia-the-ketamine-story-past-present-and-future
#6
Georges Mion
: Ketamine's history begins in the 1950s in Detroit, Michigan, at Parke-Davis Laboratories. On 26 March 1956, Harold V. Maddox synthesised phencyclidine or PCP. Domino studied PCP effects in animals and in 1958, Greifenstein made the first trials of PCP in humans under the name of Sernyl. Sernyl did not cause depression of cardiovascular and respiratory functions, but elicited severe excitation with a very prolonged postoperative recovery. Because of its psychedelic effects, it became a street drug under the name of 'angel dust' and was placed on schedule II of Federal Controlled Substance Act (CSA) in 1978...
July 20, 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28730896/cannabinoid-hyperemesis-syndrome-potential-mechanisms-for-the-benefit-of-capsaicin-and-hot-water-hydrotherapy-in-treatment
#7
John R Richards, Jeff M Lapoint, Guillermo Burillo-Putze
INTRODUCTION: Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. OBJECTIVES: In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation...
July 21, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28729524/cardiac-arrest-following-drug-abuse-with-intravenous-tapentadol-case-report-and-literature-review
#8
Misbahuddin Khaja, George Lominadze, Konstantin Millerman
BACKGROUND Tapentadol is a centrally acting opioid analgesic, with a dual mode of action, as a norepinephrine reuptake inhibitor and an agonist of the μ-opioid receptor (MOR). Tapentadol is used for the management of musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy. CASE REPORT A 32-year-old woman attended hospital for evaluation of an intractable headache. Computed tomography and magnetic resonance imaging of the brain were negative. She was found unresponsive in the bathroom on the day following hospital admission, and despite resuscitative measures, the patient died following cardiac arrest...
July 21, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28729067/real-world-characteristics-and-outcomes-of-patients-with-metastatic-castration-resistant-prostate-cancer-receiving-chemotherapy-versus-androgen-receptor-targeted-therapy-after-failure-of-first-line-androgen-receptor-targeted-therapy-in-the-community-setting
#9
William K Oh, Raymond Miao, Francis Vekeman, Jennifer Sung, Wendy Y Cheng, Marjolaine Gauthier-Loiselle, Ravinder Dhawan, Mei Sheng Duh
BACKGROUND: In metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequences are unknown. We assessed second-line taxane (TT) versus androgen receptor-targeted therapy (ART), after initial ART failure, in United States oncology community practices. PATIENTS AND METHODS: Using electronic medical records, patients with mCRPC receiving first-line ART and second-line therapy (TT, ART) were identified. Response and overall survival (OS) were evaluated from second-line therapy initiation...
June 19, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28726402/opioid-receptor-modulators-with-a-cinnamyl-group
#10
Lokesh Ravilla, N Venkata Subba Naidu, Shalini Dogra, Deepmala Umrao, Prem N Yadav, Ansuman Biswas, Daliah Michael, Kanagaraj Sekar, Kuppuswamy Nagarajan
To obtain selective and potent opioid receptor ligands, we synthesized dehydro derivatives of alvimopan and found compound (28f), a selective but modest affinity MOR antagonist, weaker than alvimopan (1). We replaced the aryl piperidine unit by an aryl piperazine to obtain the 1-(α-carboxycinnamyl)-4-arylpiperazines like (13h), which to our surprise had no MOR or DOR activity but was a KOR agonist with moderate affinity. In contrast, literature examples of aryl piperazines (4) and (5) were reported to be pan opioid receptor antagonists, while (6) was a MOR agonist...
July 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28726190/effect-of-peripheral-%C3%AE-%C3%AE-and-%C3%AE%C2%BA-opioid-ligands-on-the-development-of-tolerance-to-ethanol-induced-analgesia
#11
S K Sudakov, E V Alekseeva, G A Nazarova
We studied the rate of development of tolerance to the ethanol-induced analgesia under the effect of μ-, δ-, and κ-opioid agonists and antagonists not crossing the blood-brain barrier and rapidly inactivated by gastric and duodenal proteolytic enzymes. Activation of gastric κ-opioid receptors eliminated the analgesic effect of ethanol and accelerated the development of tolerance to ethanol-induced analgesia. In contrast, activation of gastric μ-opioid receptors decelerated the development of this tolerance...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28725181/impact-of-proestrus-on-gene-expression-in-the-medial-preoptic-area-of-mice
#12
Csaba Vastagh, Zsolt Liposits
The antero-ventral periventricular zone (AVPV) and medial preoptic area (MPOA) have been recognized as gonadal hormone receptive regions of the rodent brain that-via wiring to gonadotropin-releasing hormone (GnRH) neurons-contribute to orchestration of the preovulatory GnRH surge. We hypothesized that neural genes regulating the induction of GnRH surge show altered expression in proestrus. Therefore, we compared the expression of 48 genes obtained from intact proestrous and metestrous mice, respectively, by quantitative real-time PCR (qPCR) method...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28722022/opioid-release-after-high-intensity-interval-training-in-healthy-human-subjects
#13
Tiina Saanijoki, Lauri Tuominen, Jetro J Tuulari, Lauri Nummenmaa, Eveliina Arponen, Kari Kalliokoski, Jussi Hirvonen
Central opioidergic mechanisms may modulate the positive effects of physical exercise such as mood elevation and stress reduction. How exercise intensity and concomitant affective changes affect central opioidergic responses is unknown. We studied the effects of acute physical exercise on the cerebral μ-opioid receptors (MOR) of 22 healthy recreationally active males using positron emission tomography (PET) and the MOR-selective radioligand [(11)C]carfentanil. MOR binding was measured in three conditions on separate days: after a 60-min aerobic moderate-intensity exercise session, after a high-intensity interval training (HIIT) session, and after rest...
July 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28721822/opioid-antagonists-for-pharmacological-treatment-of-gambling-disorder-are-they-relevant
#14
Caroline Victorri-Vigneau, Andrew Spiers, Pascal Caillet, Mélanie Bruneau, Gaëlle Challet-Bouju, Marie Grall-Bronnec
Background To date, no drugs have been approved for gambling disorder. Numerous publications have described the value of opioid antagonists. Indeed, the mesocorticolimbic dopaminergic pathway has been suggested as the underlying cause of reward-seeking behaviour, and it is modulated by the opioid system. Objective This study aims to evaluate the relevance of opioid antagonists for treating GD. Method A systematic literature review was conducted. A search of the PubMed electronic database, PsycINFO and the Cochrane Systematic Review Database without any limits was performed...
July 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28719458/acupuncture-for-chronic-pain-an-update-and-critical-overview
#15
Changshik Yin, Thomas E Buchheit, Jongbae J Park
PURPOSE OF REVIEW: Acupuncture is now recommended for several chronic pain conditions. Despite supportive evidence of its effectiveness, this ancient approach is often misunderstood, and may still be underused in mainstream practice. A critical review on its effectiveness and practice integration, and mechanisms of action is essential to the medical community that is continuing to seek nonopioid therapies for chronic pain. RECENT FINDINGS: Mounting evidence supports the effectiveness of acupuncture to treat chronic low back, neck, shoulder, and knee pain, as well as headaches...
July 15, 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28718638/semisynthesis-and-kappa-opioid-receptor-activity-of-derivatives-of-columbin-a-furanolactone-diterpene
#16
Anil Yilmaz, Rachel Saylor Crowley, Alexander M Sherwood, Thomas E Prisinzano
Columbin (1) is a furanolactone diterpene isolated from the roots of Jateorhiza and Tinospora species. These species generally grow in Asia and Africa and have been used in folk medicine for their apparent analgesic and antipyretic activities. Columbin (1) is of particular interest due to its structural similarity to the known kappa-opioid receptor (KOR) agonist salvinorin A. Given that the KOR is of interest in the study of many serious diseases, such as anxiety, depression, and drug addiction, obtaining natural or semisynthetic molecules with KOR activity recently has gained much interest...
July 18, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28716934/sigma-1-receptors-control-immune-driven-peripheral-opioid-analgesia-during-inflammation-in-mice
#17
Miguel A Tejada, Angeles Montilla-García, Shane J Cronin, Domagoj Cikes, Cristina Sánchez-Fernández, Rafael González-Cano, M Carmen Ruiz-Cantero, Josef M Penninger, José M Vela, José M Baeyens, Enrique J Cobos
Sigma-1 antagonism potentiates the antinociceptive effects of opioid drugs, so sigma-1 receptors constitute a biological brake to opioid drug-induced analgesia. The pathophysiological role of this process is unknown. We aimed to investigate whether sigma-1 antagonism reduces inflammatory pain through the disinhibition of the endogenous opioidergic system in mice. The selective sigma-1 antagonists BD-1063 and S1RA abolished mechanical and thermal hyperalgesia in mice with carrageenan-induced acute (3 h) inflammation...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716608/opioidergic-and-dopaminergic-modulation-of-cost-benefit-decision-making-in-long-evans-rats
#18
Ileana Morales, Paul J Currie, Timothy D Hackenberg, Raúl Pastor
Eating disorders are associated with impaired decision-making and dysfunctional reward-related neurochemistry. The present study examined the potential contributions of dopamine and opioid signaling to these processes using two different decision-making tasks. In one task, Long Evans Rats chose between working for a preferred food (high-carbohydrate banana-flavored sucrose pellets) by lever pressing on a progressive-ratio schedule of reinforcement vs. obtaining less preferred laboratory chow that was concurrently available...
July 14, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28714716/cb%C3%A2-receptor-antagonism-in-the-bed-nucleus-of-the-stria-terminalis-interferes-with-affective-opioid-withdrawal-in-rats
#19
Kiri L Wills, Marieka V DeVuono, Cheryl L Limebeer, Kiran Vemuri, Alexandros Makriyannis, Linda A Parker
The bed nucleus of the stria terminalis (BNST) is a region of the extended amygdala that is implicated in addiction, anxiety, and stress related behaviors. This region has been identified in mediating the aversive state of naloxone-precipitated morphine withdrawal (MWD) and cannabinoid Type I (CB1) receptors have been found to modulate neurotransmission within this region. Previous findings suggest that the CB1 antagonist/inverse agonist, AM251, administered systemically or by infusion into the central nucleus of the amygdala (CeA) prevented the aversive affective properties of MWD as measured by conditioned place aversion learning...
August 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28705439/activation-of-nociceptin-orphanin-fq-receptors-inhibits-contextual-fear-memory-reconsolidation
#20
Khaoula Rekik, Raquel Faria Da Silva, Morgane Colom, Salvatore Pacifico, Nurulain T Zaveri, Girolamo Calo', Claire Rampon, Bernard Frances, Lionel Mouledous
Several neuropeptidergic systems act as modulators of cognitive performances. Among them, nociceptin, an opioid-like peptide also known as orphanin FQ (N/OFQ), has recently gained attention. Stimulation of its receptor, the N/OFQ opioid receptor (NOP), which is expressed in brain regions involved in emotion, memory and stress response, has inhibitory effects on the acquisition and/or consolidation of spatial and emotional memory in rodents. Recently, N/OFQ was also proposed to be linked to the pathogenesis of Post-Traumatic Stress Disorder in humans...
July 10, 2017: Neuropharmacology
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