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https://www.readbyqxmd.com/read/29055101/substance-p-and-dopamine-interact-to-modulate-the-distribution-of-delta-opioid-receptors-on-cholinergic-interneurons-in-the-striatum
#1
Emily Heath, Billy Chieng, Macdonald J Christie, Bernard W Balleine
It recently been demonstrated that predictive learning induces a persistent accumulation of delta-opioid receptors (DOPr's) at the somatic membrane of cholinergic interneurons (CINs) in the nucleus accumbens shell (Nac-S). This accumulation is required for predictive learning to influence subsequent choice between goal-directed actions. The current experiments investigated the local neurochemical events responsible for this translocation. We found that (1) local administration of substance P into multiple striatal sub-territories induced DOPr translocation and (2) that this effect was mediated by the NK1 receptor, likely through its expression on CINs...
October 20, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29055075/association-between-genetic-polymorphisms-and-pain-sensitivity-in-patients-with-hip-osteoarthritis
#2
Anne E Olesen, Lecia M Nielsen, Søren Feddersen, Joachim Erlenwein, Frank Petzke, Michael Przemeck, Lona L Christrup, Asbjørn M Drewes
BACKGROUND: Factors such as age, gender and genetic polymorphisms may explain individual difference in pain phenotype. Genetic associations to pain sensitivity have previously been investigated in osteoarthritis patients with focus on the P2X7, TRPV1 and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system...
October 20, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/29054455/dadle-enhances-viability-and-anti-inflammatory-effect-of-human-mscs-subjected-to-serum-free-apoptotic-condition-in-part-via-the-dor-pi3k-akt-pathway
#3
L Vinod Kumar Reddy, Dwaipayan Sen
AIM: Nutritional deprivation and inflammation-rich zones are the major causative reasons for poor survivability of transplanted mesenchymal stem cells (MSCs). Therefore in the present study, we demonstrated the cytoprotective and anti-inflammatory effects of activated delta (δ)-opioid receptor (DOR) with synthetic peptide [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) treatment on human MSCs cultured in serum-starved condition. MAIN METHODS: Cell viability was measured using MTT and Annexin V/PI assays...
October 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29038479/probing-ligand-recognition-of-the-opioid-pan-antagonist-at-076-at-nociceptin-kappa-mu-and-delta-opioid-receptors-through-structure-activity-relationships
#4
V Blair Journigan, Willma E Polgar, Edward W Tuan, James Lu, Pankaj R Daga, Nurulain T Zaveri
Few opioid ligands binding to the three classic opioid receptor subtypes, mu, kappa and delta, have high affinity at the fourth opioid receptor, the nociceptin/orphanin FQ receptor (NOP). We recently reported the discovery of AT-076 (1), (R)-7-hydroxy-N-((S)-1-(4-(3-hydroxyphenyl)piperidin-1-yl)-3-methylbutan-2-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, a pan antagonist with nanomolar affinity for all four subtypes. Since AT-076 binds with high affinity at all four subtypes, we conducted a structure-activity relationship (SAR) study to probe ligand recognition features important for pan opioid receptor activity, using chemical modifications of key pharmacophoric groups...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29032758/multifaceted-effects-of-delta-opioid-receptors-and-dadle-in-diseases-of-the-nervous-system
#5
Jea-Young Lee, M Grant Liska, Marci Crowley, Kaya Xu, Sandra A Acosta, Cesar V Borlongan, Vivian A Guedes
The opioid system is considered a potential therapeutic target in a variety of neurological disorders. Delta opioid receptors (DOPs) are broadly expressed in the brain, and their activation protects cells from hypoxic/ischemic insults by counteracting disruptions of ionic homeostasis and initiating neuroprotective pathways. The DOP agonist D-Ala2-D-Leu2-Enkephalin (DADLE) promotes neuronal survival, mitigates apoptotic pathways, and protects neurons and glial cells from ischemia-induced cell death, thus making DADLE a promising therapeutic option for stroke...
October 10, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29030229/elevation-of-proenkephalin-143-183-in-cerebrospinal-fluid-in-moyamoya-disease
#6
Kinya Yokoyama, Mikio Maruwaka, Kazuhiro Yoshikawa, Yoshio Araki, Sho Okamoto, Masaki Sumitomo, Akino Kawamura, Yusuke Sakamoto, Kenzo Shimizu, Takashi Izumi, Toshihiko Wakabayashi
BACKGROUND: In moyamoya disease (MMD), the causes of differences in clinical features between children and adults and of the dramatic temporal changes in moyamoya vessels are poorly understood. We previously discovered elevated levels of m/z 4588 and m/z 4473 peptides in cerebrospinal fluid (CSF) in MMD patients. This study examined the amino acid sequences of these peptides and quantified in specimens. METHODS: The m/z 4588 and m/z 4473 peptides in CSF from MMD patients were purified and concentrated by high-performance liquid chromatography and ultrafiltration...
October 10, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28993838/delta-opioid-receptor-expression-and-function-in-primary-afferent-somatosensory-neurons
#7
Amaury François, Grégory Scherrer
The functional diversity of primary afferent neurons of the dorsal root ganglia (DRG) generates a variety of qualitatively and quantitatively distinct somatosensory experiences, from shooting pain to pleasant touch. In recent years, the identification of dozens of genetic markers specifically expressed by subpopulations of DRG neurons has dramatically improved our understanding of this diversity and provided the tools to manipulate their activity and uncover their molecular identity and function. Opioid receptors have long been known to be expressed by discrete populations of DRG neurons, in which they regulate cell excitability and neurotransmitter release...
October 10, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28993835/delta-opioid-receptors-and-modulation-of-mood-and-emotion
#8
Isaac J Dripps, Emily M Jutkiewicz
Depression is a pervasive and debilitating mental disorder that is inadequately treated by current pharmacotherapies in a majority of patients. Although opioids have long been known to regulate mood states, the use of opioids to treat depression is rarely discussed. This chapter explores the preclinical and clinical evidence supporting the antidepressant-like effects of opioid ligands, and in particular, delta opioid receptor (DOR) agonists. DOR agonists have been shown to produce antidepressant-like effects in a number of animal models...
October 10, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28989282/spotlight-on-eluxadoline-for-the-treatment-of-patients-with-irritable-bowel-syndrome-with-diarrhea
#9
REVIEW
Konstantinos C Fragkos
BACKGROUND: Irritable bowel syndrome with diarrhea (IBS-D) has limited options for treatment currently, including mainly anti-motility medications, antispasmodics, and antidepressants. This review discusses the properties of a new drug, eluxadoline, a gut-targeting mu- and kappa-opioid receptor agonist and a delta-opioid receptor antagonist, and its efficacy and safety in patients with IBS-D. MATERIALS AND METHODS: A systematic review of the literature was undertaken to identify studies that had investigated eluxadoline as a treatment in IBS-D...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/28934264/profiling-molecular-factors-associated-with-pyknosis-and-developmental-arrest-induced-by-an-opioid-receptor-antagonist-and-dihydroartemisinin-in-plasmodium-falciparum
#10
Hiroko Asahi, Shin-Ichi Inoue, Mamoru Niikura, Keisuke Kunigo, Yutaka Suzuki, Fumie Kobayashi, Fujiro Sendo
Malaria continues to be a devastating disease, largely caused by Plasmodium falciparum infection. We investigated the effects of opioid and cannabinoid receptor antagonists on the growth of intraerythrocytic P. falciparum. The delta opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) and the cannabinoid receptor antagonists rimonaband and SR144528 caused growth arrest of the parasite. Notably BNTX and the established antimalarial drug dihydroartemisinin induced prominent pyknosis in parasite cells after a short period of incubation...
2017: PloS One
https://www.readbyqxmd.com/read/28923348/stimulation-of-accumbal-gabaa-receptors-inhibits-delta2-but-not-delta1-opioid-receptor-mediated-dopamine-efflux-in-the-nucleus-accumbens-of-freely-moving-rats
#11
Yuri Aono, Yuri Kiguchi, Yuriko Watanabe, John L Waddington, Tadashi Saigusa
The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABAA receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABAA receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABAA receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis...
September 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28864205/the-delta-opioid-receptor-agonist-knt-127-in-the-prelimbic-medial-prefrontal-cortex-attenuates-veratrine-induced-anxiety-like-behaviors-in-mice
#12
Akiyoshi Saitoh, Satoshi Suzuki, Akinobu Soda, Masanori Ohashi, Misa Yamada, Jun-Ichiro Oka, Hiroshi Nagase, Mitsuhiko Yamada
We previously reported that systemic administration of the selective delta opioid receptor (DOP) agonist KNT-127 produces potent anxiolytic-like effects in rats. Although a higher distribution pattern of DOPs was reported in the prelimbic medial prefrontal cortex (PL-PFC) of rodents, the role of DOPs in PL-PFC and in anxiolytic-like effects have not been well examined. Recently, we demonstrated that activation of PL-PFC with the sodium channel activator veratrine increases glutamatergic neurotransmission and produces anxiety-like behaviors in mice...
January 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28855588/morphine-activation-of-mu-opioid-receptors-causes-disinhibition-of-neurons-in-the-ventral-tegmental-area-mediated-by-%C3%AE-arrestin2-and-c-src
#13
Fiona A Bull, Daniel T Baptista-Hon, Jeremy J Lambert, Wendy Walwyn, Tim G Hales
The tyrosine kinase, c-Src, participates in mu opioid receptor (MOP) mediated inhibition in sensory neurons in which β-arrestin2 (β-arr2) is implicated in its recruitment. Mice lacking β-arr2 exhibit increased sensitivity to morphine reinforcement; however, whether β-arr2 and/or c-Src participate in the actions of opioids in neurons within the reward pathway is unknown. It is also unclear whether morphine acts exclusively through MOPs, or involves delta opioid receptors (DOPs). We examined the involvement of MOPs, DOPs, β-arr2 and c-Src in the inhibition by morphine of GABAergic inhibitory postsynaptic currents (IPSCs) recorded from neurons in the mouse ventral tegmental area...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844812/antidepressant-like-effects-of-3-carboxamido-seco-nalmefene-3cs-nalmefene-a-novel-opioid-receptor-modulator-in-a-rat-ifn-%C3%AE-induced-depression-model
#14
Charlotte K Callaghan, Jennifer Rouine, Reginald L Dean, Brian I Knapp, Jean M Bidlack, Daniel R Deaver, Shane M O'Mara
Patients receiving the cytokine immunotherapy, interferon-alpha (IFN-α) frequently present with neuropsychiatric consequences and cognitive impairments. Patients (25-80%) report symptoms of depression, including, anhedonia, irritability, fatigue and impaired motivation. Our lab has previously demonstrated treatment (170,000IU/kg sc, 3 times per week for 4weeks) of the pro-inflammatory cytokine, IFN-α, induced a depressive phenotype in rats in the forced swim test (FST). Here, we examine the biological mechanisms underlying behavioral changes induced by IFN-α, which may be reflective of mechanisms underlying inflammation associated depression...
August 24, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28841868/a-systematic-review-of-the-effectiveness-of-policies-restricting-access-to-pregabalin
#15
Brett R Stacey, Jonathan Liss, Regina Behar, Alesia Sadosky, Bruce Parsons, Elizabeth T Masters, Patrick Hlavacek
BACKGROUND: Formularies often employ restriction policies to reduce pharmacy costs. Pregabalin, an alpha-2-delta ligand, is approved for treatment of fibromyalgia (FM); neuropathic pain (NeP) due to postherpetic neuralgia (PHN), diabetic peripheral neuropathy (pDPN), spinal cord injury; and as adjunct therapy for partial onset seizures. Pregabalin is endorsed as first-line therapy for these indications by several US and EU medical professional societies. However, restriction policies such as prior authorization (PA) and step therapy (ST) often favor less costly generic pain medications over pregabalin...
August 25, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28836121/nerve-decompression-improves-spinal-synaptic-plasticity-of-opioid-receptors-for-pain-relief
#16
To-Jung Tseng, Ming-Ling Yang, Yu-Lin Hsieh, Miau-Hwa Ko, Sung-Tsang Hsieh
Nerve decompression is an essential therapeutic strategy for pain relief clinically; however, its potential mechanism remains poorly understood. Opioid analgesics acting on opioid receptors (OR) within the various regions of the nervous system have been used widely for pain management. We therefore hypothesized that nerve decompression in a neuropathic pain model of chronic constriction injury (CCI) improves the synaptic OR plasticity in the dorsal horn, which is in response to alleviate pain hypersensitivity...
August 23, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28830758/the-medicinal-chemistry-and-neuropharmacology-of-kratom-a-preliminary-discussion-of-a-promising-medicinal-plant-and-analysis-of-its-potential-for-abuse
#17
REVIEW
Andrew C Kruegel, Oliver Grundmann
The leaves of Mitragyna speciosa (commonly known as kratom), a tree endogenous to parts of Southeast Asia, have been used traditionally for their stimulant, mood-elevating, and analgesic effects and have recently attracted significant attention due to increased use in Western cultures as an alternative medicine. The plant's active alkaloid constituents, mitragynine and 7-hydroxymitragynine, have been shown to modulate opioid receptors, acting as partial agonists at mu-opioid receptors and competitive antagonists at kappa- and delta-opioid receptors...
August 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28830121/drugged-driving-in-wisconsin-oral-fluid-versus-blood
#18
Lorrine D Edwards, Katherine L Smith, Theodore Savage
A pilot project was conducted in Dane County, Wisconsin, to evaluate the frequency of individuals driving under the influence of drugs (DUID). Evidentiary blood specimens, collected from subjects arrested for Operating While Intoxicated (OWI), were compared to oral fluid (OF) results obtained with the Alere DDS2®, a handheld screening device. The project objectives were to evaluate (i) the Alere DDS2® for use by police officers in the field, (ii) the frequency of individuals DUID and drugs combined with alcohol among OWI cases, (iii) the differences between detecting drugs in OF and in blood, and (iv) the effect of the laboratory drug testing cancellation policy (LCP) when the blood alcohol concentration (BAC) exceeds 0...
July 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28807672/pharmacological-characterization-of-novel-synthetic-opioids-nso-found-in-the-recreational-drug-marketplace
#19
REVIEW
Michael H Baumann, Susruta Majumdar, Valerie Le Rouzic, Amanda Hunkele, Rajendra Uprety, Xi Ping Huang, Jin Xu, Bryan L Roth, Ying-Xian Pan, Gavril W Pasternak
Novel synthetic opioids (NSO) are increasingly encountered in illicit heroin and counterfeit pain pills. Many NSO are resurrected from older biomedical literature or patent applications, so limited information is available about their biological effects. Here we examined the pharmacology of three structurally-distinct NSO found in the recreational drug market: N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylbutyramide (butyrylfentanyl), 3,4-dichloro-N-[(1R,2R)-2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) and 1-cyclohexyl-4-(1,2-diphenylethyl)piperazine (MT-45)...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28782637/synthesis-and-activity-of-opioid-peptidomimetics-with-%C3%AE-2-and-%C3%AE-3-amino-acids
#20
Katarzyna Gach-Janczak, Justyna Piekielna-Ciesielska, Anna Adamska-Bartłomiejczyk, Renata Perlikowska, Rafał Kruszyński, Alicja Kluczyk, Julia Krzywik, Jarosław Sukiennik, Maria Camilla Cerlesi, Girolamo Calo, Andrzej Wasilewski, Marta Zielińska, Anna Janecka
Morphiceptin (Tyr-Pro-Phe-Pro-NH2) is a selective ligand of the mu opioid receptor, an important target in pain regulation. In this study, morphiceptin was modified at positions 2 or 3 by introduction of β(2)- or β(3)-amino acids and additionally in position 1 by replacing Tyr by Dmt (2',6'-dimethyltyrosine), which resulted in obtaining enzymatically stable analogs with mixed opioid receptor affinity profiles. An analog of the sequence Dmt-d-Ala-(R)-β(2)-1-Nal-Pro-NH2 [Nal=3-(1-naphthyl)-alanine] showed very high activity at the mu and delta receptors in the calcium mobilization functional test but did not cross the artificial membrane imitating the blood-brain barrier...
August 3, 2017: Peptides
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