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opioid genetics

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https://www.readbyqxmd.com/read/28074005/synergistic-regulation-of-serotonin-and-opioid-signaling-contributes-to-pain-insensitivity-in-nav1-7-knockout-mice
#1
Jörg Isensee, Leonhardt Krahé, Katharina Moeller, Vanessa Pereira, Jane E Sexton, Xiaohui Sun, Edward Emery, John N Wood, Tim Hucho
Genetic loss of the voltage-gated sodium channel Nav1.7 (Nav1.7(-/-)) results in lifelong insensitivity to pain in mice and humans. One underlying cause is an increase in the production of endogenous opioids in sensory neurons. We analyzed whether Nav1.7 deficiency altered nociceptive heterotrimeric guanine nucleotide-binding protein-coupled receptor (GPCR) signaling, such as initiated by GPCRs that respond to serotonin (pronociceptive) or opioids (antinociceptive), in sensory neurons. We found that the nociceptive neurons of Nav1...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28071341/identification-of-novel-hits-as-highly-prospective-dual-agonists-for-mu-and-kappa-opioid-receptors-an-integrated-in-silico-approach
#2
Indrani Bera, Mrinal Vishwas Marathe, Pavan V Payghan, Nanda Ghoshal
Opioid agonists are used clinically for the treatment of acute and chronic pain, however, their clinical use is limited due to the presence of undesired side effects. Dual agonists, simultaneously targeting mu and kappa opioid receptors, show fewer side effects than that of selective agonists. In the present work, 2D- and 3D- Quantitative Structure Activity Relationship studies were performed on a series of aminomorphinan derivatives as dual agonists, using a wide range of descriptors. The aim of the study was to identify the structural requirements for the activity of these compounds towards mu and kappa opioid receptors and using the models, with best external predictability, for predicting the activities of new hits obtained from shape based virtual screening of drug like compounds from ZINC database...
January 10, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28057931/the-oprm1-a118g-polymorphism-modulates-the-descending-pain-modulatory-system-for-individual-pain-experience-in-young-women-with-primary-dysmenorrhea
#3
Shyh-Yuh Wei, Li-Fen Chen, Ming-Wei Lin, Wei-Chi Li, Intan Low, Ching-Ju Yang, Hsiang-Tai Chao, Jen-Chuen Hsieh
The mu-opioid receptor (OPRM1) A118G polymorphism underpins different pain sensitivity and opioid-analgesic outcome with unclear effect on the descending pain modulatory system (DPMS). Primary dysmenorrhea (PDM), the most prevalent gynecological problem with clear painful and pain free conditions, serves as a good clinical model of spontaneous pain. The objective of this imaging genetics study was therefore to explore if differences in functional connectivity (FC) of the DPMS between the OPRM1 A118G polymorphisms could provide a possible explanation for the differences in pain experience...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28045073/insensitivity-to-pain-induced-by-a-potent-selective-closed-state-nav1-7-inhibitor
#4
M Flinspach, Q Xu, A D Piekarz, R Fellows, R Hagan, A Gibbs, Y Liu, R A Neff, J Freedman, W A Eckert, M Zhou, R Bonesteel, M W Pennington, K A Eddinger, T L Yaksh, M Hunter, R V Swanson, A D Wickenden
Pain places a devastating burden on patients and society and current pain therapeutics exhibit limitations in efficacy, unwanted side effects and the potential for drug abuse and diversion. Although genetic evidence has clearly demonstrated that the voltage-gated sodium channel, Nav1.7, is critical to pain sensation in mammals, pharmacological inhibitors of Nav1.7 have not yet fully recapitulated the dramatic analgesia observed in Nav1.7-null subjects. Using the tarantula venom-peptide ProTX-II as a scaffold, we engineered a library of over 1500 venom-derived peptides and identified JNJ63955918 as a potent, highly selective, closed-state Nav1...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28035534/oprd1-genetic-variation-and-human-disease
#5
Richard C Crist, Toni-Kim Clarke
The OPRD1 gene encodes the delta-opioid receptor, which has multiple functions including regulating reward pathways. The gene contains more than 2,000 verified genetic variants but only 2 currently have evidence for specific functions: rs1042114 disrupts maturation of the receptor and rs569356 affects OPRD1 expression. These polymorphisms and others in the gene have been found to be associated with human diseases. The most reproducible data are associations between opioid addiction and three variants in intron 1 (rs2236861, rs2236857, and rs3766951), which have been described in a number of independent populations...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035528/delta-opioid-receptors-learning-and-motivation
#6
L P Pellissier, C N Pujol, J A J Becker, J Le Merrer
Delta opioid receptor (DOR) displays a unique, highly conserved, structure and an original pattern of distribution in the central nervous system, pointing to a distinct and specific functional role among opioid peptide receptors. Over the last 15 years, in vivo pharmacology and genetic models have allowed significant advances in the understanding of this role. In this review, we will focus on the involvement of DOR in modulating different types of hippocampal- and striatal-dependent learning processes as well as motor function, motivation, and reward...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28012859/endogenous-opiates-and-behavior-2015
#7
REVIEW
Richard J Bodnar
This paper is the thirty-eighth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2015 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia, stress and social status, tolerance and dependence, learning and memory, eating and drinking, drug abuse and alcohol, sexual activity and hormones, pregnancy, development and endocrinology, mental illness and mood, seizures and neurologic disorders, electrical-related activity and neurophysiology, general activity and locomotion, gastrointestinal, renal and hepatic functions, cardiovascular responses, respiration and thermoregulation, and immunological responses...
December 22, 2016: Peptides
https://www.readbyqxmd.com/read/27996183/relationship-between-abcb1-polymorphisms-and-cold-pain-sensitivity-among-healthy-opioid-naive-malay-males
#8
Zalina Zahari, Chee Siong Lee, Muslih Abdulkarim Ibrahim, Nurfadhlina Musa, Mohd Azhar Mohd Yasin, Yeong Yeh Lee, Soo Choon Tan, Nasir Mohamad, Rusli Ismail
BACKGROUND: Endogenous and exogenous opioids are substrates of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses. We investigated the relationship between ABCB1 polymorphisms and cold pain sensitivity among healthy males. METHODS: Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT)...
December 20, 2016: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/27988368/conditioned-flavor-preferences-in-animals-merging-pharmacology-brain-sites-and-genetic-variance
#9
Richard J Bodnar
The elucidation of the behavioral, neurochemical, neuroanatomical and genetic substrates mediating the development of conditioned flavor preferences (CFP) is one of the multi-faceted scientific contributions that Dr. Anthony Sclafani has made to the study of food intake. This review summarizes the results of thirty-five publications over nearly twenty years of collaborations between the Sclafani and Bodnar laboratories. This includes the different approaches employed to study the orosensory (flavor-flavor) and post-ingestive (flavor-nutrient) processes underlying CFP including its acquisition (learning) and expression...
December 14, 2016: Appetite
https://www.readbyqxmd.com/read/27964861/pain-opioids-and-sleep-implications-for-restless-legs-syndrome-treatment
#10
Claudia Trenkwalder, Walter Zieglgänsberger, Sam H Ahmedzai, Birgit Högl
Opioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described...
November 5, 2016: Sleep Medicine
https://www.readbyqxmd.com/read/27955884/pharmacogenetics-guided-analgesics-in-major-abdominal-surgery-further-benefits-within-an-enhanced-recovery-protocol
#11
Anthony J Senagore, Bradley J Champagne, Eslam Dosokey, Justin Brady, Scott R Steele, Harry L Reynolds, Sharon L Stein, Conor P Delaney
OBJECTIVE: Effective, narcotic sparing analgesia is a major component of Enhanced Recovery Protocols (ERP), however the risk of poor analgesia and opioid related side effects (ORADE) remains an issue related to poor outcomes and satisfaction, and is strongly related to the risk of narcotic dependence after surgery. A variety of genes can impact narcotic and non-steroidal (NSAID) drug efficacy including: the CYP family (drug metabolism-narcotics and NSAID), or COMT/ABCB1/OPRM1 (functional receptor and transport activity for analgesia vs side effects)...
November 22, 2016: American Journal of Surgery
https://www.readbyqxmd.com/read/27940188/effectiveness-of-adjunctive-personalised-psychosocial-intervention-for-non-response-to-opioid-agonist-treatment-study-protocol-for-a-pragmatic-randomised-controlled-trial
#12
John Marsden, Garry Stillwell, Jennifer Hellier, Anne Marie Brown, Sarah Byford, Michael Kelleher, Joanne Kelly, Caroline Murphy, James Shearer, Luke Mitcheson
INTRODUCTION: Opioid use disorder (OUD) is a debilitating and relapsing psychiatric disorder; opioid agonist therapy (OAT) is the front-line, evidence-supported treatment. A substantial number of patients relapse or continue to use heroin or other illicit drugs during OAT. There is considerable heterogeneity in the OAT-resistant sub-population, with many behavioural moderators of treatment response. We have developed a personalised psychosocial intervention (PSI) targeting these individuals...
December 8, 2016: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/27935783/the-role-of-pharmacogenomics-in-anesthesia-pharmacology
#13
Brett Morgan, Edwin N Aroke, Jennifer Dungan
The field of pharmacogenomics seeks to identify the impact of genetic variants on drug dosing, response, metabolism, and safety outcomes. The narrow therapeutic indices for anesthesia drugs, variability of patient responses to anesthesia, and the risks associated with surgery make anesthetics and the perioperative period prime targets for pharmacogenetic research. Anesthesia providers strive to optimize anesthesia delivery and patient outcomes and to specifically reduce anesthesia-related risks and negative outcomes...
January 2017: Annual Review of Nursing Research
https://www.readbyqxmd.com/read/27899885/interacting-cannabinoid-and-opioid-receptors-in-the-nucleus-accumbens-core-control-adolescent-social-play
#14
Antonia Manduca, Olivier Lassalle, Marja Sepers, Patrizia Campolongo, Vincenzo Cuomo, Giovanni Marsicano, Brigitte Kieffer, Louk J M J Vanderschuren, Viviana Trezza, Olivier J J Manzoni
Social play behavior is a highly rewarding, developmentally important form of social interaction in young mammals. However, its neurobiological underpinnings remain incompletely understood. Previous work has suggested that opioid and endocannabinoid neurotransmission interact in the modulation of social play. Therefore, we combined behavioral, pharmacological, electrophysiological, and genetic approaches to elucidate the role of the endocannabinoid 2-arachidonoylglycerol (2-AG) in social play, and how cannabinoid and opioid neurotransmission interact to control social behavior in adolescent rodents...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27883323/association-of-single-nucleotide-polymorhism-c3435t-in-the-abcb1-gene-with-opioid-sensitivity-in-treatment-of-postoperative-pain
#15
Vanja Dzambazovska-Trajkovska, Jordan Nojkov, Andrijan Kartalov, Biljana Kuzmanovska, Tatjana Spiroska, Redzep Seljmani, Gjorgji Trajkovski, Nadica Matevska-Geshkovska, Aleksandar Dimovski
BACKGROUND: The minimal effective analgesic concentration of opioids required for satisfactory analgesia may differ significantly among the patients. Genetic factors may contribute to the variable response to opioids by affecting their pharmacokinetics or pharmacodynamics. METHODS: Ninety nine patients undergoing abdominal surgery with colorectal anastomosis because of colorectal carcinoma were enrolled in the present study. C34535T was genotyped in all subjects and the patients were divided into three groups according to their genotype: CC-wild type homozygous, CT-mutant heterozygous and TT-mutant homozygous...
November 1, 2016: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/27870427/understanding-the-broad-influence-of-sex-hormones-and-sex-differences-in-the-brain
#16
REVIEW
Bruce S McEwen, Teresa A Milner
Sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes, where they are associated with presynaptic terminals, mitochondria, spine apparatus, and postsynaptic densities. Sex hormone receptors also are found in glial cells...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27861439/trends-in-tramadol-pharmacology-metabolism-and-misuse
#17
Karen Miotto, Arthur K Cho, Mohamed A Khalil, Kirsten Blanco, Jun D Sasaki, Richard Rawson
Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects...
January 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27842787/precision-medicine-in-toxicology
#18
REVIEW
Daniel A Schwarz, M P George, Martin H Bluth
Precision medicine applies primarily to pharmacokinetics in toxicology. Mastering hepatic metabolism through an understanding of the genetics behind Phase I, or oxidation/reduction and some Phase II, or conjugation, enhances the scientific and clinical application of common drug toxicology. This review includes basic hepatic metabolism, the common substrates, inducers and inhibitors of cytochrome P450 along with genetic variants behind the enzymes. Detailed metabolism of commonly measured opioids in clinical practice is provided...
December 2016: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/27833495/postoperative-pain-management-of-liver-transplantation-in-cystic-fibrosis-is-it-time-to-start-us-guided-neuraxial-blocks
#19
M Piazza, G Martucci, A Arcadipane
Cystic fibrosis (CF) is the most common life-limiting genetic disease in Caucasians. Declining lung function is the principal cause of death, but liver involvement can lead to the need for liver transplantation. General anesthesia has detrimental effects on pulmonary function, increasing perioperative morbidity and mortality in CF patients. Regional anesthetic techniques improve outcomes by reducing anesthetic drugs and administration of opioids, and hastening extubation, awakening, and restarting respiratory of physiotherapy...
October 2016: Saudi Journal of Anaesthesia
https://www.readbyqxmd.com/read/27819122/erratum-to-carriers-of-genetic-variants-in-the-hnf1a-gene-are-more-common-among-dead-opioid-addicts-than-among-living-addicts
#20
Anh Nguyen, Tore B Stage, Søren Feddersen, Dorte J Christoffersen, Mette Marie H Christensen, Per Damkier, Jørgen L Thomsen, Kim Brøsen
No abstract text is available yet for this article.
November 7, 2016: European Journal of Clinical Pharmacology
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