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Pharmacological treatment of addiction

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https://www.readbyqxmd.com/read/29740351/pain-therapy-guided-by-purpose-and-perspective-in-light-of-the-opioid-epidemic
#1
REVIEW
Amie L Severino, Arash Shadfar, Joshua K Hakimian, Oliver Crane, Ganeev Singh, Keith Heinzerling, Wendy M Walwyn
Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29715300/public-versus-internal-conceptions-of-addiction-an-analysis-of-internal-philip-morris-documents
#2
Jesse Elias, Yogi Hale Hendlin, Pamela M Ling
BACKGROUND: Tobacco addiction is a complex, multicomponent phenomenon stemming from nicotine's pharmacology and the user's biology, psychology, sociology, and environment. After decades of public denial, the tobacco industry now agrees with public health authorities that nicotine is addictive. In 2000, Philip Morris became the first major tobacco company to admit nicotine's addictiveness. Evolving definitions of addiction have historically affected subsequent policymaking. This article examines how Philip Morris internally conceptualized addiction immediately before and after this announcement...
May 2018: PLoS Medicine
https://www.readbyqxmd.com/read/29698859/design-synthesis-and-pharmacological-evaluation-of-alk-and-hsp90-dual-inhibitors-bearing-resorcinol-and-2-4-diaminopyrimidine-motifs
#3
Kaijun Geng, Hongchun Liu, Zilan Song, Chi Zhang, Minmin Zhang, Hong Yang, Jingchen Cao, Meiyu Geng, Aijun Shen, Ao Zhang
Rather than by directly focusing on the ever-changing ALK mutants, here we report an alternative strategy to overcome the drug resistance caused by treatment of ALK inhibitors by developing ALK and Hsp90 dual targeting inhibitors. Since Hsp90 is a molecular chaperone that regulates the maturation, activation and stability of numerous "client proteins" including ALK, dual targeting ALK and Hsp90 may bring more benefits and efficacy against drug resistance of ALK inhibitors. By using our previously developed ALK inhibitor 6 and the clinical Hsp90 inhibitors AUY922 or AT13387 as the templates, we developed several series of resorcinol tethered 2,4-diaminopyrimidines as ALK/Hsp90 dual inhibitors bearing various linkers at different linking sites...
April 11, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29680151/vmat2-inhibitors-and-the-path-to-ingrezza-valbenazine
#4
Nicole D Harriott, John P Williams, Evan B Smith, Haig P Bozigian, Dimitri E Grigoriadis
The dopaminergic system plays a key role in the central nervous system, regulating executive function, arousal, reward, and motor control. Dysregulation of this critical monoaminergic system has been associated with diseases of the central nervous system including schizophrenia, Parkinson's disease, and disorders such as attention deficit hyperactivity disorders and addiction. Drugs that modify the dopaminergic system by modulating the activity of dopamine have been successful in demonstrating clinical efficacy by providing treatments for these diseases...
2018: Progress in Medicinal Chemistry
https://www.readbyqxmd.com/read/29675582/multifunctional-opioid-ligands
#5
Jessica P Anand, Deanna Montgomery
The opioid receptor system plays a major role in the regulation of mood, reward, and pain. The opioid receptors therefore make attractive targets for the treatment of many different conditions, including pain, depression, and addiction. However, stimulation or blockade of any one opioid receptor type often leads to on-target adverse effects that limit the clinical utility of a selective opioid agonist or antagonist. Literature precedent suggests that the opioid receptors do not act in isolation and that interactions among the opioid receptors and between the opioid receptors and other proteins may produce clinically useful targets...
April 20, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29674970/hypothesis-the-psychedelic-ayahuasca-heals-traumatic-memories-via-a-sigma-1-receptor-mediated-epigenetic-mnemonic-process
#6
Antonio Inserra
Ayahuasca ingestion modulates brain activity, neurotransmission, gene expression and epigenetic regulation. N,N -Dimethyltryptamine (DMT, one of the alkaloids in Ayahuasca) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation. Simultaneously, monoamine oxidase inhibitors (MAOIs) also present in Ayahuasca prevent the degradation of DMT. One peculiarity of SIGMAR1 activation and MAOI activity is the reversal of mnemonic deficits in pre-clinical models...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29669731/involvement-of-activated-brain-stress-responsive-systems-in-excessive-and-relapse-alcohol-drinking-in-rodent-models-implications-for-therapeutics
#7
Yan Zhou, Mary Jeanne Kreek
Addictive diseases, including addiction to alcohol pose massive public health costs. Addiction is a chronic relapsing disease, caused by both the direct effects induced by drugs and persistent neuroadaptations at several (molecular, cellular and behavioral) levels. These drug-type specific neuro-adaptations are brought on largely by the reinforcing effects of drugs on the central nervous system and environment, including stress. Results from animal experiments have demonstrated important interactions between alcohol and the stress responsive systems...
April 18, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29666833/resolving-the-coffey-paradox-what-does-the-androgen-receptor-do-in-normal-vs-malignant-prostate-epithelial-cells
#8
REVIEW
John T Isaacs
Donald Straley Coffey completed his 85 year life's journey on November 9, 2017. In his wake, he left a legion of inspired and loyal students, fellows, and faculty colleagues from all over the world to carry on his passion both for life in general and his 50 year quest to conquer cancer. Early in his career, Dr. Coffey developed a series of animal models to study how androgen regulates the growth of both normal and abnormal prostatic epithelium. As part of these early studies, Dr. Coffey uncovered a paradox in that anti-androgen treatment given at the "wrong" time paradoxically enhanced, not inhibited, normal prostate growth...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29649583/noradrenergic-%C3%AE-receptor-antagonism-in-the-basolateral-amygdala-impairs-reconsolidation-but-not-extinction-of-alcohol-self-administration-intra-bla-propranolol-impairs-reconsolidation-of-alcohol-self-administration
#9
Rose Chesworth, Laura H Corbit
A critical barrier to recovery from alcohol addiction is relapse propensity. Alcohol cues can trigger relapse, and pharmacologically facilitating processes such as extinction, which decreases cue associations, may help prevent relapse. The noradrenergic system mediates extinction learning for alcohol; however, the neural locus of this effect is unknown. This study sought to determine whether the basolateral amygdala (BLA), a region critical for fear extinction, also mediates extinction of alcohol seeking. Hooded Wistar rats (N = 12-15 per experiment) were implanted with bilateral cannula targeting the BLA and trained to lever press for 10% ethanol during auditory or visual cues...
April 9, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29643474/histone-deacetylase-6-controls-notch3-trafficking-and-degradation-in-t-cell-acute-lymphoblastic-leukemia-cells
#10
Marica Pinazza, Margherita Ghisi, Sonia Minuzzo, Valentina Agnusdei, Gianluca Fossati, Vincenzo Ciminale, Laura Pezzè, Yari Ciribilli, Giorgia Pilotto, Carolina Venturoli, Alberto Amadori, Stefano Indraccolo
Several studies have revealed that endosomal sorting controls the steady-state levels of Notch at the cell surface in normal cells and prevents its inappropriate activation in the absence of ligands. However, whether this highly dynamic physiologic process can be exploited to counteract dysregulated Notch signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by aberrant Notch signaling, sustained by activating mutations in Notch1 as well as overexpression of Notch3, a Notch paralog physiologically subjected to lysosome-dependent degradation in human cancer cells...
April 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29627310/understanding-antidepressant-discontinuation-syndrome-ads-through-preclinical-experimental-models
#11
REVIEW
Konstantin N Zabegalov, Tatiana O Kolesnikova, Sergey L Khatsko, Andrey D Volgin, Oleg A Yakovlev, Tamara G Amstislavskaya, Polina A Alekseeva, Darya A Meshalkina, Ashton J Friend, Wandong Bao, Konstantin A Demin, Raul R Gainetdinov, Allan V Kalueff
Antidepressant drugs are currently one of the most prescribed medications. In addition to treatment resistance and side effects of antidepressants, their clinical use is further complicated by antidepressant discontinuation syndrome (ADS). ADS is a common problem in patients following the interruption, dose reduction, or discontinuation of antidepressant drugs. Clinically, ADS resembles a classical drug withdrawal syndrome, albeit differing from it because antidepressants generally do not induce addiction. The growing clinical importance and prevalence of ADS necessitate novel experimental (animal) models of this disorder...
April 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29625852/double-blind-evaluation-of-homeopathy-on-cocaine-craving-a-randomized-controlled-pilot-study
#12
Ubiratan Cardinalli Adler, Ana Carolina Acorinte, Fernando Oliveira Calzavara, Adriano André da Silva, Amarilys de Toledo Cesar, Maristela Schiabel Adler, Edson Zangiacomi Martinez, José Carlos Fernandes Galduróz
BACKGROUND: Brazil is among the nations with the greatest rates of annual cocaine usage. Pharmacological treatment of cocaine addiction is still limited, opening space for nonconventional interventions. Homeopathic Q-potencies of opium and Erythroxylum coca have been tested in the integrative treatment of cocaine craving among homeless addicts, but this setting had not proven feasible, due to insufficient recruitment. OBJECTIVE: This study investigates the effectiveness and tolerability of homeopathic Q-potencies of opium and E...
March 30, 2018: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29616150/methadone-treatment-of-opiate-addiction-a-systematic-review-of-comparative-studies
#13
REVIEW
Shahid Ali, Barira Tahir, Shagufta Jabeen, Madeeha Malik
Opiate misuse is a chronic relapsing disease that has become an epidemic in the United States. Methadone is the mainstay of treatment for opiate addiction and has been researched widely. Recently, new avenues of treatment have been researched and developed. The objective of this review is to study methadone in comparison to other pharmacological options available or being considered for opiate addiction treatment through a methodical search and review of evidence provided by recent clinical trials conducted in this regard...
July 2017: Innovations in Clinical Neuroscience
https://www.readbyqxmd.com/read/29615715/blocking-interleukin-4-enhances-efficacy-of-vaccines-for-treatment-of-opioid-abuse-and-prevention-of-opioid-overdose
#14
Megan Laudenbach, Federico Baruffaldi, Christine Robinson, Philipp Carter, Davis Seelig, Carly Baehr, Marco Pravetoni
Vaccines offer an option to treat heroin and prescription opioid abuse and prevent fatal overdoses. Opioid vaccines elicit antibodies that block opioid distribution to the brain and reduce opioid-induced behavioral effects and toxicity. The major limitation to the translation of addiction vaccines is that efficacy is observed only in subjects achieving optimal drug-specific serum antibody levels. This study tested whether efficacy of a vaccine against oxycodone is increased by immunomodulators targeting key cytokine signaling pathways involved in B and T cell lymphocyte activation...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29593494/antiepileptogenic-effect-of-subchronic-palmitoylethanolamide-treatment-in-a-mouse-model-of-acute-epilepsy
#15
Julia M Post, Sebastian Loch, Raissa Lerner, Floortje Remmers, Ermelinda Lomazzo, Beat Lutz, Laura Bindila
Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA])...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29571016/the-role-of-nutrients-in-the-pathogenesis-and-treatment-of-migraine-headaches-review
#16
REVIEW
Elyas Nattagh-Eshtivani, Mahmood Alizadeh Sani, Monireh Dahri, Faezeh Ghalichi, Abed Ghavami, Pishva Arjang, Ali Tarighat-Esfanjani
OBJECTIVE: Migraine as a disabling neurovascular disease affects 6% of men and 18% of women worldwide. The deficiency of many nutrients including magnesium, niacin, riboflavin, cobalamin, coenzymes Q10, carnitine, α-lipoic acid and vitamin D is associated with migraine. Some researchers postulate that mitochondrial dysfunction and impaired antioxidant status can cause migraine. Also increase in homocysteine level can lead to migraine attacks; therefore, some Nutraceuticals play a vital role in migraine prevention...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29569907/design-and-mechanism-of-gaba-aminotransferase-inactivators-treatments-for-epilepsies-and-addictions
#17
Richard B Silverman
When the brain concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) diminishes below a threshold level, the excess neuronal excitation can lead to convulsions. This imbalance in neurotransmission can be corrected by inhibition of the enzyme γ-aminobutyric acid aminotransferase (GABA-AT), which catalyzes the conversion of GABA to the excitatory neurotransmitter l-glutamic acid. It also has been found that raising GABA levels can antagonize the rapid elevation and release of dopamine in the nucleus accumbens, which is responsible for the reward response in addiction...
March 23, 2018: Chemical Reviews
https://www.readbyqxmd.com/read/29561705/hsp90-inhibition-targets-autophagy-and-induces-a-casp9-dependent-resistance-mechanism-in-nsclc
#18
Jie Han, Leslie A Goldstein, Wen Hou, Suman Chatterjee, Timothy F Burns, Hannah Rabinowich
Macroautophagy/autophagy has emerged as a resistance mechanism to anticancer drug treatments that induce metabolic stress. Certain tumors, including a subset of KRAS-mutant NSCLCs have been shown to be addicted to autophagy, and potentially vulnerable to autophagy inhibition. Currently, autophagy inhibition is being tested in the clinic as a therapeutic component for tumors that utilize this degradation process as a drug resistance mechanism. The current study provides evidence that HSP90 (heat shock protein 90) inhibition diminishes the expression of ATG7, thereby impeding the cellular capability of mounting an effective autophagic response in NSCLC cells...
March 21, 2018: Autophagy
https://www.readbyqxmd.com/read/29546602/the-many-faces-of-apomorphine-lessons-from-the-past-and-challenges-for-the-future
#19
REVIEW
Manon Auffret, Sophie Drapier, Marc Vérin
Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson's disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its synthesis, pharmacological development, and numerous indications in human and veterinary medicine, in light of its most recent uses and newest challenges...
March 15, 2018: Drugs in R&D
https://www.readbyqxmd.com/read/29535626/trace-amine-associated-receptor-1-taar1-modulation-of-food-reward
#20
REVIEW
Catherine F Moore, Valentina Sabino, Pietro Cottone
Eating disorders and some forms of obesity are characterized by addictive-like, compulsive eating behavior which contains numerous similarities with compulsive drug use. Food intake is in part mediated by reward and reinforcement processes that can become dysregulated in these disorders. Additionally, impairments in inhibitory control regulation of reward-related responding can cause or further exacerbate binge and compulsive eating. Dysfunctions in two neurotransmitter systems in the mesocorticolimbic pathway, dopamine and glutamate, are thought to contribute to maladaptive eating behaviors...
2018: Frontiers in Pharmacology
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