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Delta opioid receptor

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https://www.readbyqxmd.com/read/29779230/role-of-mu-but-not-delta-or-kappa-opioid-receptors-in-context-induced-reinstatement-of-oxycodone-seeking
#1
Jennifer M Bossert, Jennifer K Hoots, Ida Fredriksson, Sweta Adhikary, Michelle Zhang, Marco Venniro, Yavin Shaham
Relapse to nonmedical use of prescription opioids often occurs after exposure to places previously associated with drug use. Here, we describe a rat model of context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction-induced abstinence. We also determined the role of mu, delta, and kappa opioid receptors (MOR, DOR, KOR) in this reinstatement. We trained rats to self-administer oxycodone for 6 h/d in Context A; lever pressing was paired with a discrete cue...
May 19, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29771142/the-development-of-a-mouse-model-of-mtbi-induced-post-traumatic-migraine-and-identification-of-the-delta-opioid-receptor-as-a-novel-therapeutic-target
#2
Laura S Moye, Madeline L Novack, Alycia F Tipton, Harish Krishnan, Subhash C Pandey, Amynah Aa Pradhan
Background Post-traumatic headache is the most common and long-lasting impairment observed following mild traumatic brain injury, and frequently has migraine-like characteristics. The mechanisms underlying progression from mild traumatic brain injury to post-traumatic headache are not fully understood. The aim of this study was to develop a mouse model of post-traumatic headache and identify mechanisms and novel targets associated with this disorder. Methods We combined the closed head weight-drop method and the nitroglycerin chronic migraine model...
January 1, 2018: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29768254/neuroprotection-against-hypoxic-ischemic-injury-%C3%AE-opioid-receptors-and-bdnf-trkb-pathway
#3
Shiying Sheng, Jingzhong Huang, Yi Ren, Feng Zhi, Xuansong Tian, Guoqiang Wen, Guanghong Ding, Terry C Xia, Fei Hua, Ying Xia
The delta-opioid receptor (DOR) is one of three classic opioid receptors in the opioid system. It was traditionally thought to be primarily involved in modulating the transmission of messages along pain signaling pathway. Although there were scattered studies on its other neural functions, inconsistent results and contradicting conclusions were found in past literatures, especially in terms of DOR's role in a hypoxic/ischemic brain. Taking inspiration from the finding that the turtle brain exhibits a higher DOR density and greater tolerance to hypoxic/ischemic insult than the mammalian brain, we clarified DOR's specific role in the brain against hypoxic/ischemic injury and reconciled previous controversies in this aspect...
May 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29734749/synthesis-and-structure-activity-relationships-of-cis-n-normetazocine-based-lp1-derivatives
#4
Lorella Pasquinucci, Carmela Parenti, Emanuele Amata, Zafiroula Georgoussi, Paschalina Pallaki, Valeria Camarda, Girolamo Calò, Emanuela Arena, Lucia Montenegro, Rita Turnaturi
(−)- cis - N -Normetazocine represents a rigid scaffold able to mimic the tyramine moiety of endogenous opioid peptides, and the introduction of different N -substituents influences affinity and efficacy of respective ligands at MOR (mu opioid receptor), DOR (delta opioid receptor), and KOR (kappa opioid receptor). We have previously identified LP1, a MOR/DOR multitarget opioid ligand, with an N -phenylpropanamido substituent linked to (−)- cis - N -Normetazocine scaffold. Herein, we report the synthesis, competition binding and calcium mobilization assays of new compounds 10 ⁻ 16 that differ from LP1 by the nature of the N -substituent...
May 5, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29729777/methadone-maximizing-safety-and-efficacy-for-pain-control-in-patients-with-cancer
#5
REVIEW
Mary Lynn McPherson, Ryan C Costantino, Alexandra L McPherson
Methadone is a valuable opioid in the management of patients who have cancer with pain. Methadone is a mu-, kappa-, and delta-opioid agonist, and an N-methyl-D-aspartate receptor antagonist. These mechanisms of action make methadone an attractive option for complex pain syndromes. It is critically important that providers consider a patient's risk status before beginning methadone. Careful consideration must be given to dosing methadone in both opioid-naïve and opioid-tolerant patients, with vigilant monitoring for therapeutic effectiveness and potential toxicity until the patient achieves steady state...
June 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/29727730/dor-agonist-snc-80-exhibits-anti-parkinsonian-effect-via-downregulating-upr-oxidative-stress-signals-and-inflammatory-response-in-vivo
#6
Erfath Thanjeem Begum M, Dwaipayan Sen
The pathophysiology of Parkinson's disease exhibit imperative roles in unfolded protein response stress-induced oxidative stress and inflammation in general. Although, delta opioid receptor (DOR), has been found to represent anti-parkinsonian effect at behavioral level, its underlying mechanism remains elusive till date. In the present study the role of DOR agonist, SNC-80 and the consorted molecular mechanisms, which translates to behavioral recuperation, has been delineated. In order to mimic PD, mice were intra-peritoneally injected with MPTP, following exposure to SNC-80 and L-DOPA to elucidate amelioration of the MPTP-induced behavioral impairments...
May 1, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29722902/tolerance-to-high-internalizing-delta-opioid-receptor-agonist-is-critically-mediated-by-arrestin-2
#7
Ana Vicente-Sanchez, Isaac J Dripps, Alycia F Tipton, Heba Akbari, Areeb Akbari, Emily M Jutkiewicz, Amynah A Pradhan
BACKGROUND AND PURPOSE: Delta opioid receptor (δOR) agonists are potent antihyperalgesics in chronic pain models, but tolerance develops after prolonged use. Previous evidence indicates that distinct forms of tolerance occur depending on the internalization properties of δOR agonists. Due to the importance of arrestins in receptor internalization, we investigated the role of arrestin 2 (β-arrestin 1) in mediating the development of tolerance induced by high- and low-internalizing δOR agonists...
May 3, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29713172/gender-specific-association-of-functional-prodynorphin-68-bp-repeats-with-cannabis-exposure-in-an-african-american-cohort
#8
Vadim Yuferov, Eduardo R Butelman, Mary Jeanne Kreek
Background: Cannabis use disorders (CUDs) cause substantial neuropsychiatric morbidity and comorbidity. There is evidence for gender-based differences in CUDs, for instance, a greater prevalence in males than in females. The main active component of cannabis is delta 9-tetrahydrocannabinol (delta 9-THC), a partial agonist of the cannabinoid type 1 receptor. Preclinical studies show that genetic or pharmacological manipulation of the kappa opioid receptor/dynorphin system modulates the effects of delta 9-THC...
2018: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29686629/critical-role-for-g-i-o-protein-activity-in-the-dorsal-striatum-in-the-reduction-of-voluntary-alcohol-intake-in-c57bl-6-mice
#9
Meridith T Robins, Terrance Chiang, Kendall L Mores, Doungkamol Alongkronrusmee, Richard M van Rijn
The transition from non-dependent alcohol use to alcohol dependence involves increased activity of the dorsal striatum. Interestingly, the dorsal striatum expresses a large number of inhibitory G-protein-coupled receptors (GPCRs), which when activated may inhibit alcohol-induced increased activity and can decrease alcohol consumption. Here, we explore the hypothesis that dorsal striatal Gi/o -protein activation is sufficient to reduce voluntary alcohol intake. Using a voluntary, limited-access, two-bottle choice, drink-in-the-dark model of alcohol (10%) consumption, we validated the importance of Gi/o signaling in this region by locally expressing neuron-specific, adeno-associated-virus encoded Gi/o -coupled muscarinic M4 designer receptors exclusively activated by designer drugs (DREADD) in the dorsal striatum and observed a decrease in alcohol intake upon DREADD activation...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29684591/in-vitro-and-in-vivo-activity-of-opioid-cyclopeptide-with-mu-delta-agonist-profile-biased-toward-%C3%AE-arrestin
#10
Katarzyna Gach-Janczak, Justyna Piekielna-Ciesielska, Anna Adamska-Bartłomiejczyk, Karol Wtorek, Federica Ferrari, Girolamo Calo, Agata Szymaszkiewicz, Joanna Piasecka-Zelga, Anna Janecka
Replacement of the tyrosine residue in the mu-selective opioid ligand Tyr-c[D-Lys-Phe-Asp]NH2 with 2',6'-dimethyltyrosine (Dmt) produced a cyclopeptide Dmt-c[D-Lys-Phe-Asp]NH2 with mu/delta opioid receptor agonist profile. This new analog showed improved antinociception in the hot-plate test as compared to the parent but also significantly inhibited the gastrointestinal transit. Using the bioluminescence resonance energy transfer (BRET) assay it was shown that this analog was biased toward β-arrestin.
April 20, 2018: Peptides
https://www.readbyqxmd.com/read/29681795/delta-opioid-receptor-signaling-promotes-resilience-to-stress-under-the-repeated-social-defeat-paradigm-in-mice
#11
Mathilde S Henry, Kanchan Bisht, Nathalie Vernoux, Louis Gendron, Angélica Torres-Berrio, Guy Drolet, Marie-Ève Tremblay
The adaptation to chronic stress is highly variable across individuals. Resilience to stress is a complex process recruiting various brain regions and neurotransmitter systems. The aim of this study was to investigate the involvement of endogenous opioid enkephalin (ENK) signaling in the development of stress resilience in mice. The translational model of repeated social defeat (RSD) stress was selected to mimic the unpredictable disruptions of daily life and induce resilience or vulnerability to stress. As in humans, adult C57BL/6J mice demonstrated a great variability in their response to stress under this paradigm...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29677442/synthesis-and-pharmacological-evaluation-of-novel-c-8-substituted-tetrahydroquinolines-as-balanced-affinity-mu-delta-opioid-ligands-for-the-treatment-of-pain
#12
Anthony F Nastase, Nicholas W Griggs, Jessica P Anand, Thomas J Fernandez, Aubrie A Harland, Tyler J Trask, Emily M Jutkiewicz, John R Traynor, Henry I Mosberg
The use of opioids for the treatment of pain, while largely effective, is limited by detrimental side effects including analgesic tolerance, physical dependence, and euphoria, which may lead to opioid abuse. Studies have shown that compounds with a -opioid receptor (MOR) agonist/-opioid receptor (DOR) antagonist profile reduce or eliminate some of these side effects including development of tolerance and dependence. Herein we report the synthesis and pharmacological evaluation of a series of tetrahydroquinoline-based peptidomimetics with substitutions at the C-8 position...
April 20, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29651609/the-delta-opioid-peptide-dadle-represses-hypoxia-reperfusion-mimicked-stress-mediated-apoptotic-cell-death-in-human-mesenchymal-stem-cells-in-part-by-downregulating-the-unfolded-protein-response-and-ros-along-with-enhanced-anti-inflammatory-effect
#13
Madhubanti Mullick, Dwaipayan Sen
Hypoxia-reperfusion (H/R) emblems a plethora of pathological conditions which is potent in contributing to the adversities encountered by human mesenchymal stem cells (hMSCs) in post-transplant microenvironment, resulting in transplant failure. D-Alanine 2, Leucine 5 Enkephaline (DADLE)-mediated delta opioid receptor (DOR) activation is well-known for its recuperative properties in different cell types like neuronal and cardiomyocytes. In the current study its effectiveness in assuaging hMSC mortality under H/R-like insult has been delineated...
April 12, 2018: Stem Cell Reviews
https://www.readbyqxmd.com/read/29649744/synthesis-of-7%C3%AE-hydroxy-8-ketone-opioid-derivatives-with-antagonist-activity-at-mu-and-delta-opioid-receptors
#14
Tiina J Ahonen, Maiju Rinne, Peter Grutschreiber, Kert Mätlik, Mikko Airavaara, Dieter Schaarschmidt, Heinrich Lang, David Reiss, Henri Xhaard, Claire Gaveriaux-Ruff, Jari Yli-Kauhaluoma, Vânia M Moreira
Despite extensive years of research, the direct oxidation of the 7,8-double bond of opioids has so far received little attention and knowledge about the effects of this modification on activity at the different opioid receptors is scarce. We herein report that potassium permanganate supported on iron(II) sulfate heptahydrate can be used as a convenient oxidant in the one-step, heterogeneous conversion of Δ7,8 -opioids to the corresponding 7β-hydroxy-8-ketones. Details of the reaction mechanism are given and the effects of the substituent at position 6 of several opioids on the reaction outcome is discussed...
March 26, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29627297/neuropharmacological-effects-of-essential-oil-from-the-leaves-of-croton-conduplicatus-kunth-and-possible-mechanisms-of-action-involved
#15
Raimundo Gonçalves de Oliveira Júnior, Christiane Adrielly Alves Ferraz, Juliane Cabral Silva, Roxana Braga de Andrade Teles, Mariana Gama E Silva, Tâmara Coimbra Diniz, Uiliane Soares Dos Santos, Ana Valéria Vieira de Souza, Carlos Eduardo Pereira Nunes, Marcos José Salvador, Vitor Prates Lorenzo, Lucindo José Quintans Junior, Jackson Roberto Guedes da Silva Almeida
ETHNOPHARMACOLOGICAL RELEVANCE: Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as "quebra-faca". In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. AIM OF THE STUDY: In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia...
April 5, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29616344/novel-pharmacological-nonopioid-therapies-in-chronic-pain
#16
REVIEW
Alan David Kaye, Elyse M Cornett, Brendon Hart, Shilpadevi Patil, Andrew Pham, Matthew Spalitta, Kenneth F Mancuso
PURPOSE OF REVIEW: Opioid use and abuse has led to a worldwide opioid epidemic. And while opioids are clinically useful when appropriately indicated, they are associated with a wide range of dangerous side effects and whether they are effective at treating or eliminating chronic pain is controversial. There has long been a need for the development of nonopioid alternative treatments for patients that live in pain, and until recently, only a few effective treatments were available. Today, there are a wide range of nonopioid treatments available including NSAIDs, acetaminophen, corticosteroids, nerve blocks, SSRIs, neurostimulators, and anticonvulsants...
April 3, 2018: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/29589835/snc80-and-naltrindole-modulate-voltage-dependent-sodium-potassium-and-calcium-channels-via-a-putatively-delta-opioid-receptor-independent-mechanism
#17
Lucia Moravčíková, Jana Královičová, Ľubica Lacinová
SNC80 was designed as a highly selective nonpeptide delta opioid receptor (DOR) agonist. Antidepressant-like and antinociceptive effects of this compound were demonstrated in animal models. Naltrindole was synthetized as a highly selective DOR antagonist. Its antitussive and antinociceptive effects were reported. Observed effects of SNC80 and naltrindole may be accompanied by changes in neuronal excitability including modulation of voltage-dependent ion channels. We investigated possible DOR-independent modulation of neuronal sodium, calcium and potassium currents by both agents...
March 28, 2018: General Physiology and Biophysics
https://www.readbyqxmd.com/read/29579315/co-expression-of-%C3%AE-and-%C3%A2-opioid-receptors-by-mouse-colonic-nociceptors
#18
Raquel Guerrero-Alba, Eduardo Emmanuel Valdez-Morales, Nestor Nivardo Jiménez-Vargas, Romke Bron, Daniel Poole, David Reed, Joel Castro, Melissa Campaniello, Patrick A Hughes, Stuart M Brierley, Nigel Bunnett, Alan E Lomax, Stephen Vanner
BACKGROUND AND PURPOSE: To better understand opioid signaling in visceral nociceptors, we examined the expression and selective activation of mu (MOR) and delta opioid receptors (DOR) by dorsal root ganglia (DRG) neurons innervating the mouse colon. EXPERIMENTAL APPROACH: DRG neurons projecting to the colon were identified by retrograde tracing. DOR-GFP reporter mice, in situ hybridization, single-cell RT-PCR, and MOR-specific antibodies were used to characterize expression of MOR and DOR...
March 26, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29576387/functional-divergence-of-delta-and-mu-opioid-receptor-organization-in-cns-pain-circuits
#19
Dong Wang, Vivianne L Tawfik, Gregory Corder, Sarah A Low, Amaury François, Allan I Basbaum, Grégory Scherrer
Cellular interactions between delta and mu opioid receptors (DORs and MORs), including heteromerization, are thought to regulate opioid analgesia. However, the identity of the nociceptive neurons in which such interactions could occur in vivo remains elusive. Here we show that DOR-MOR co-expression is limited to small populations of excitatory interneurons and projection neurons in the spinal cord dorsal horn and unexpectedly predominates in ventral horn motor circuits. Similarly, DOR-MOR co-expression is rare in parabrachial, amygdalar, and cortical brain regions processing nociceptive information...
March 14, 2018: Neuron
https://www.readbyqxmd.com/read/29572653/delta-mu-opioid-receptor-interactions-in-operant-conditioning-assays-of-pain-depressed-responding-and-drug-induced-rate-suppression-assessment-of-therapeutic-index-in-male-sprague-dawley-rats
#20
Katherine Cone, Janell Lanpher, Abigail Kinens, Philomena Richard, Sarah Couture, Rebecca Brackin, Emily Payne, Kylee Harrington, Kenner C Rice, Glenn W Stevenson
RATIONALE AND OBJECTIVES: Although delta/mu receptor interactions vary as a function of behavioral endpoint, there have been no assessments of these interactions using assays of pain-depressed responding. This is the first report of delta/mu interactions using an assay of pain-depressed behavior. METHODS: A mult-cycle FR10 operant schedule was utilized in the presence of (nociception) and in the absence of (rate suppression) a lactic acid inflammatory pain-like manipulation...
March 23, 2018: Psychopharmacology
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