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Pharmacological treatment of addiction

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https://www.readbyqxmd.com/read/28319052/a-tail-of-opioid-receptor-variants
#1
Stephanie Puig, Howard B Gutstein
Opioids are the gold-standard treatment for severe pain. However, potentially life-threatening side effects decrease the safety and effectiveness of these compounds. The addiction liability of these drugs has led to the current epidemic of opioid abuse in the US. Extensive research efforts have focused on trying to dissociate the analgesic properties of opioids from their undesirable side effects. Splice variants of the mu opioid receptor (MOR), which mediates opioid actions, have unique pharmacological properties and anatomic distributions that make them attractive candidates for therapeutic pain relief...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28315272/sigma-receptors-and-substance-use-disorders
#2
Valentina Sabino, Callum Hicks, Pietro Cottone
Thanks to advances in neuroscience, addiction is now recognized as a chronic brain disease with genetic, developmental, and cultural components. Drugs of abuse, including alcohol, are able to produce significant neuroplastic changes responsible for the profound disturbances shown by drug addicted individuals. The current lack of efficacious pharmacological treatments for substance use disorders has encouraged the search for novel and more effective pharmacotherapies. Growing evidence strongly suggests that Sigma Receptors are involved in the addictive and neurotoxic properties of abused drugs, including cocaine , methamphetamine , and alcohol...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28302509/binding-mode-analyses-of-nap-derivatives-as-mu-opioid-receptor-selective-ligands-through-docking-studies-and-molecular-dynamics-simulation
#3
Huiqun Wang, Saheem A Zaidi, Yan Zhang
Mu opioid receptor selective antagonists are highly desirable because of their utility as pharmacological probes for receptor characterization and functional studies. Furthermore, the mu opioid receptors act as an important target in drug abuse and addiction treatment. Previously, we reported NAP as a novel lead compound with high selectivity and affinity towards the mu opioid receptor. Based on NAP, we have synthesized its derivatives and further characterized their binding affinities and selectivity towards the receptor...
March 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28285325/mglu1-receptor-as-a-drug-target-for-treatment-of-substance-use-disorders-time-to-gather-stones-together
#4
REVIEW
Olga A Dravolina, Edwin Zvartau, Wojciech Danysz, Anton Y Bespalov
Modulation of the mGlu1 receptor was repeatedly shown to inhibit various phenomena associated with exposure to abused drugs. Efficacy in preclinical models was observed with both positive and negative allosteric modulators (PAMs and NAMs, respectively) using essentially non-overlapping sets of experimental methods. Taken together, these data indicate that the mGlu1 receptor certainly plays a significant role in the plasticity triggered by the exposure to abused drugs and is involved in the maintenance of drug-seeking and drug-taking behaviors...
March 11, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28277828/cultivating-change-door-to-door-educational-outreach-to-improve-prescribing-practices-in-rural-veterans-with-ptsd
#5
Macgregor Montaño, Nancy C Bernardy, Kathleen Sherrieb
BACKGROUND: Clinical guidelines for the management of posttraumatic stress disorder (PTSD) recommend against the use of benzodiazepines. Benzodiazepines and PTSD are both associated with addiction-related risks. VA prescribing trends show continued use of benzodiazepines and polysedative use in veterans with PTSD, particularly in rural areas. The authors examine the use of an educational intervention to improve pharmacologic management of veterans with PTSD in rural clinics. METHODS: The VA Academic Detailing Service Informatics Toolset provides prescribing, demographic and risk factor data for veterans with PTSD treated at the White River Junction VA Medical Center (WRJ VA) and affiliated rural clinics in Vermont and New Hampshire...
March 9, 2017: Substance Abuse
https://www.readbyqxmd.com/read/28272130/pharmacological-treatment-of-adhd-in-addicted-patients-what-does-the-literature-tell-us
#6
Pieter-Jan Carpentier, Frances R Levin
LEARNING OBJECTIVES: After participating in this activity, learners should be better able to:• Evaluate pharmacologic treatment of attention deficit/hyperactivity disorder (ADHD) in patients with substance use disorder (SUD) • Assess the causes of the diminished efficacy of ADHD medication in patients with comorbid SUD OBJECTIVE: Substance use disorder (SUD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur, and the presence of ADHD complicates the treatment of the addiction...
March 2017: Harvard Review of Psychiatry
https://www.readbyqxmd.com/read/28267152/effects-of-naltrexone-are-influenced-by-childhood-adversity-during-negative-emotional-processing-in-addiction-recovery
#7
G Savulich, R Riccelli, L Passamonti, M Correia, J F W Deakin, R Elliott, R S A Flechais, A R Lingford-Hughes, J McGonigle, A Murphy, D J Nutt, C Orban, L M Paterson, L J Reed, D G Smith, J Suckling, R Tait, E M Taylor, B J Sahakian, T W Robbins, K D Ersche
Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited...
March 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28265714/a-short-history-of-the-5-ht2c-receptor-from-the-choroid-plexus-to-depression-obesity-and-addiction-treatment
#8
REVIEW
Jose M Palacios, Angel Pazos, Daniel Hoyer
This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5-HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [(3)H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography...
March 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28251946/-heterodimeric-d1-d2-dopamine-receptors-a-review
#9
REVIEW
N L Vekshina, P K Anokhin, A G Veretinskaya, I Yu Shamakina
This review summarizes modern data on the structure and functions ofheteromersformed by D1 and D2 dopamine receptors focusing on their role in the mechanisms of drug dependence. This article discusses potential functional significance of heterodimeric D1-D2 dopamine receptorsdue to their localization in the brain as well as unique pharmacological propertiesversus constituent monomers. It is shown that heteromerization results in dramatic changes in activated signaling pathways compare to the corresponding monomers...
January 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28214183/-misuse-and-dependence-on-prescription-opioids-prevention-identification-and-treatment
#10
B Rolland, D Bouhassira, N Authier, M Auriacombe, V Martinez, P Polomeni, G Brousse, R Schwan, P Lack, J Bachellier, S Rostaing, P Bendimerad, P Vergne-Salle, M Dematteis, S Perrot
Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28214075/asymmetric-total-synthesis-of-tetrahydroprotoberberine-derivatives-and-evaluation-of-their-binding-affinities-at-dopamine-receptors
#11
David Y W Lee, Jing Liu, Shuzhen Zhang, Peng Huang, Lee-Yuan Liu-Chen
Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. l-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites l-ICP, l-CD, and l-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors...
January 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28213190/n-acetylcysteine-for-treating-cocaine-addiction-a-systematic-review
#12
REVIEW
Marco Antonio Nocito Echevarria, Tassio Andrade Reis, Giulianno Ruffo Capatti, Victor Siciliano Soares, Dartiu Xavier da Silveira, Thiago Marques Fidalgo
The aim of this paper is to extensively review the current literature available on N-acetylcysteine (NAC) treatment for cocaine dependence (clinical and experimental studies). We screened all articles published before February 2016 reporting on the use of NAC as a pharmacological intervention for cocaine dependence or discussed its potential as a therapeutic approach for cocaine dependence. We described our results qualitatively. 21 studies matched our search criteria: 6 clinical trials and 15 animal studies...
February 11, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28202458/sensitivity-to-pi3k-and-akt-inhibitors-is-mediated-by-divergent-molecular-mechanisms-in-subtypes-of-dlbcl
#13
Tabea Erdmann, Pavel Klener, James T Lynch, Michael Grau, Petra Vočková, Jan Molinsky, Diana Tuskova, Kevin Hudson, Urszula M Polanska, Michael Grondine, Michele Mayo, Beiying Dai, Matthias Pfeifer, Kristian Erdmann, Daniela Schwammbach, Myroslav Zapukhlyak, Annette M Staiger, German Ott, Wolfgang E Berdel, Barry R Davies, Francisco Cruzalegui, Marek Trneny, Peter Lenz, Simon T Barry, Georg Lenz
Activated B-cell-like (ABC) and germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL) represent the two major molecular DLBCL subtypes. They are characterized by differences in clinical course and by divergent addiction to oncogenic pathways. To determine activity of novel compounds in these two subtypes, we conducted an unbiased pharmacologic in vitro screen. The phosphatidylinositol-3-kinase (PI3K) alpha/delta (PI3Kα/δ) inhibitor AZD8835 showed marked potency in ABC DLBCL models, whereas the protein kinase B (AKT) inhibitor AZD5363 induced apoptosis in PTEN-deficient DLBCLs irrespective of their molecular subtype...
February 15, 2017: Blood
https://www.readbyqxmd.com/read/28188737/genetic-variation-in-the-behavioral-effects-of-buprenorphine-in-female-mice-derived-from-a-murine-model-of-the-oprm1-a118g-polymorphism
#14
Caroline A Browne, Rebecca L Erickson, Julie A Blendy, Irwin Lucki
Pharmacogenetic studies have identified the non-synonymous single nucleotide polymorphism (A118G) in the human mu opioid receptor (MOR) gene (OPRM1) as a critical genetic variant capable of altering the efficacy of opioid therapeutics. To date few studies have explored the potential impact of the OPRM1 A118G polymorphism on the pharmacological effects of buprenorphine (BPN), a potent MOR partial agonist and kappa opioid receptor antagonist, which is approved by the FDA for the treatment of opioid addiction and chronic pain...
February 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28187838/pharmacologic-treatment-of-opioid-addiction-during-pregnancy
#15
REVIEW
Lori Keough, Heidi Collins Fantasia
Opioid addiction during pregnancy presents a treatment challenge to clinicians and women alike. Untreated addiction can lead to poor maternal and fetal health outcomes. Medication-assisted treatment is the standard of care, and methadone is the current drug of choice for treatment. Emerging evidence also supports the use of buprenorphine during pregnancy. Both methadone and buprenorphine have risks and benefits that should be explored before initiating treatment. Clinicians who work in obstetrics and in addiction treatment can collaborate and coordinate treatment to ensure optimal maternal and fetal outcomes...
February 2017: Nursing for Women's Health
https://www.readbyqxmd.com/read/28174112/epigenetic-basis-of-the-dark-side-of-alcohol-addiction
#16
REVIEW
Subhash C Pandey, Evan J Kyzar, Huaibo Zhang
Alcoholism is a complex brain disease characterized by three distinct stages of the addiction cycle that manifest as neuroadaptive changes in the brain. One such stage of the addiction cycle is alcohol withdrawal and the negative affective states that promote drinking and maintain addiction. Repeated alcohol use, genetic predisposition to alcoholism and anxiety, and alcohol exposure during crucial developmental periods all contribute to the development of alcohol-induced withdrawal and negative affective symptoms...
February 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28152236/gender-differences-among-treatment-seeking-adults-with-cannabis-use-disorder-clinical-profiles-of-women-and-men-enrolled-in-the-achieving-cannabis-cessation-evaluating-n-acetylcysteine-treatment-accent-study
#17
Brian J Sherman, Aimee L McRae-Clark, Nathaniel L Baker, Susan C Sonne, Therese K Killeen, Kasie Cloud, Kevin M Gray
BACKGROUND AND OBJECTIVES: Recent evidence suggests that women may fare worse than men in cannabis trials with pharmacologic interventions. Identifying baseline clinical profiles of treatment-seeking cannabis-dependent adults could inform gender-specific treatment planning and development. METHODS: The current study compared baseline demographic, cannabis use, and psychiatric factors between women (n = 86) and men (n = 216) entering the Achieving Cannabis Cessation-Evaluating N-acetylcysteine Treatment (ACCENT) study, a multi-site, randomized controlled trial conducted within the National Drug Abuse Treatment Clinical Trials Network...
March 2017: American Journal on Addictions
https://www.readbyqxmd.com/read/28135387/the-opioid-epidemic-what-does-it-mean-for-nurses
#18
Laura G Leahy
The United States is facing a major crisis with the current opioid epidemic. Tens of thousands of individuals are dying each year due to abuse and misuse of heroin and prescription opiate drugs. Nurses play an integral role in these aspects of health care and offer solutions by providing education; preventive measures; treatments, including medication-assisted treatments (MATs); and ongoing recovery options for individuals with opioid use disorders. Nurses provide education, issue prescriptions and dispense medications, and provide overall physical and mental health care to patients struggling with this "disease of the brain," and with the signing of the Comprehensive Addiction and Recovery Act, advanced practice RNs will soon be able to include MATs related to buprenorphine as part of their treatment plan...
January 1, 2017: Journal of Psychosocial Nursing and Mental Health Services
https://www.readbyqxmd.com/read/28130052/pharmacological-activation-of-the-neurotensin-receptor-1-abrogates-the-methamphetamine-induced-striatal-apoptosis-in-the-mouse-brain
#19
Qingkun Liu, Ariela Hazan, Eddie Grinman, Jesus A Angulo
Methamphetamine (METH) is a widely abused psychostimulant displaying potent addictive and neurotoxic properties. METH induces neurotoxicity of dopaminergic terminals and striatal neurons in the striatum. Despite much information on neurotransmitters, the role of neuropeptides is poorly understood. In this study, we investigated the role of the neuropeptide neurotensin on the METH-induced apoptosis of some striatal neurons in mice. We observed that a single injection of METH (30 mg/kg, ip) induced the loss of approximately 15% of striatal neurons...
January 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28123023/role-of-taar1-within-the-subregions-of-the-mesocorticolimbic-dopaminergic-system-in-cocaine-seeking-behavior
#20
Jian-Feng Liu, Justin N Siemian, Robert Seaman, Yanan Zhang, Jun-Xu Li
A novel G-protein coupled receptor, trace amine-associated receptor 1 (TAAR1), has been shown to be a promising target to prevent stimulant relapse. Our recent studies showed that systemic administration of TAAR1 agonists decreased abuse-related behaviors of cocaine. However, the role of TAAR1 in specific subregions of the reward system in drug addiction is unknown. Here, using a local pharmacological activation method, we assessed the role of TAAR1 within the subregions of the mesocorticolimbic system: that is, the VTA, the prelimbic cortex (PrL), and infralimbic cortex of medial prefrontal cortex, the core and shell of NAc, BLA, and CeA, on cue- and drug-induced cocaine-seeking in the rat cocaine reinstatement model...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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